Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations
Cancer-associated fibroblasts (CAF) are a poorly characterized cell population in the context of liver cancer. Our study investigates CAF functions in intrahepatic cholangiocarcinoma (ICC), a highly desmoplastic liver tumor. Genetic tracing, single-cell RNA sequencing, and ligand-receptor analyses u...
Saved in:
| Published in | Cancer cell Vol. 39; no. 6; pp. 866 - 882.e11 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
14.06.2021
|
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Cancer-associated fibroblasts (CAF) are a poorly characterized cell population in the context of liver cancer. Our study investigates CAF functions in intrahepatic cholangiocarcinoma (ICC), a highly desmoplastic liver tumor. Genetic tracing, single-cell RNA sequencing, and ligand-receptor analyses uncovered hepatic stellate cells (HSC) as the main source of CAF and HSC-derived CAF as the dominant population interacting with tumor cells. In mice, CAF promotes ICC progression, as revealed by HSC-selective CAF depletion. In patients, a high panCAF signature is associated with decreased survival and increased recurrence. Single-cell RNA sequencing segregates CAF into inflammatory and growth factor-enriched (iCAF) and myofibroblastic (myCAF) subpopulations, displaying distinct ligand-receptor interactions. myCAF-expressed hyaluronan synthase 2, but not type I collagen, promotes ICC. iCAF-expressed hepatocyte growth factor enhances ICC growth via tumor-expressed MET, thus directly linking CAF to tumor cells. In summary, our data demonstrate promotion of desmoplastic ICC growth by therapeutically targetable CAF subtype-specific mediators, but not by type I collagen.
[Display omitted]
•The majority of CAF in ICC are derived from hepatic stellate cells•Inflammatory CAF promote ICC through HGF and its receptor MET•myCAF promote ICC through Has2/hyaluronic acid•CAF-derived type I collagen contributes to stiffness but does not promote ICC growth
Intrahepatic cholangiocarcinoma (ICC) is an extraordinarily stiff liver tumor due to abundant scar-forming cancer-associated fibroblasts (CAF). Here, Affo et al. determine the origin and functions of CAF, and uncover distinct CAF subsets, promoting ICC growth via different therapeutically targetable mediators. Thus, CAF and their mediators may serve as therapeutic targets for ICC. |
|---|---|
| AbstractList | Cancer-associated fibroblasts (CAF) are a poorly characterized cell population in the context of liver cancer. Our study investigates CAF functions in intrahepatic cholangiocarcinoma (ICC), a highly desmoplastic liver tumor. Genetic tracing, single-cell RNA sequencing, and ligand-receptor analyses uncovered hepatic stellate cells (HSC) as the main source of CAF and HSC-derived CAF as the dominant population interacting with tumor cells. In mice, CAF promotes ICC progression, as revealed by HSC-selective CAF depletion. In patients, a high panCAF signature is associated with decreased survival and increased recurrence. Single-cell RNA sequencing segregates CAF into inflammatory and growth factor-enriched (iCAF) and myofibroblastic (myCAF) subpopulations, displaying distinct ligand-receptor interactions. myCAF-expressed hyaluronan synthase 2, but not type I collagen, promotes ICC. iCAF-expressed hepatocyte growth factor enhances ICC growth via tumor-expressed MET, thus directly linking CAF to tumor cells. In summary, our data demonstrate promotion of desmoplastic ICC growth by therapeutically targetable CAF subtype-specific mediators, but not by type I collagen.Cancer-associated fibroblasts (CAF) are a poorly characterized cell population in the context of liver cancer. Our study investigates CAF functions in intrahepatic cholangiocarcinoma (ICC), a highly desmoplastic liver tumor. Genetic tracing, single-cell RNA sequencing, and ligand-receptor analyses uncovered hepatic stellate cells (HSC) as the main source of CAF and HSC-derived CAF as the dominant population interacting with tumor cells. In mice, CAF promotes ICC progression, as revealed by HSC-selective CAF depletion. In patients, a high panCAF signature is associated with decreased survival and increased recurrence. Single-cell RNA sequencing segregates CAF into inflammatory and growth factor-enriched (iCAF) and myofibroblastic (myCAF) subpopulations, displaying distinct ligand-receptor interactions. myCAF-expressed hyaluronan synthase 2, but not type I collagen, promotes ICC. iCAF-expressed hepatocyte growth factor enhances ICC growth via tumor-expressed MET, thus directly linking CAF to tumor cells. In summary, our data demonstrate promotion of desmoplastic ICC growth by therapeutically targetable CAF subtype-specific mediators, but not by type I collagen. Cancer-associated fibroblasts (CAF) are a poorly characterized cell population in the context of liver cancer. Our study investigates CAF functions in intrahepatic cholangiocarcinoma (ICC), a highly desmoplastic liver tumor. Genetic tracing, single-cell RNA sequencing, and ligand-receptor analyses uncovered hepatic stellate cells (HSC) as the main source of CAF and HSC-derived CAF as the dominant population interacting with tumor cells. In mice, CAF promotes ICC progression, as revealed by HSC-selective CAF depletion. In patients, a high panCAF signature is associated with decreased survival and increased recurrence. Single-cell RNA sequencing segregates CAF into inflammatory and growth factor-enriched (iCAF) and myofibroblastic (myCAF) subpopulations, displaying distinct ligand-receptor interactions. myCAF-expressed hyaluronan synthase 2, but not type I collagen, promotes ICC. iCAF-expressed hepatocyte growth factor enhances ICC growth via tumor-expressed MET, thus directly linking CAF to tumor cells. In summary, our data demonstrate promotion of desmoplastic ICC growth by therapeutically targetable CAF subtype-specific mediators, but not by type I collagen. [Display omitted] •The majority of CAF in ICC are derived from hepatic stellate cells•Inflammatory CAF promote ICC through HGF and its receptor MET•myCAF promote ICC through Has2/hyaluronic acid•CAF-derived type I collagen contributes to stiffness but does not promote ICC growth Intrahepatic cholangiocarcinoma (ICC) is an extraordinarily stiff liver tumor due to abundant scar-forming cancer-associated fibroblasts (CAF). Here, Affo et al. determine the origin and functions of CAF, and uncover distinct CAF subsets, promoting ICC growth via different therapeutically targetable mediators. Thus, CAF and their mediators may serve as therapeutic targets for ICC. Cancer-associated fibroblasts (CAF) are a poorly characterized cell population in the context of liver cancer. Our study investigates CAF functions in intrahepatic cholangiocarcinoma (ICC), a highly desmoplastic liver tumor. Genetic tracing, single-cell RNA sequencing, and ligand-receptor analyses uncovered hepatic stellate cells (HSC) as the main source of CAF and HSC-derived CAF as the dominant population interacting with tumor cells. In mice, CAF promotes ICC progression, as revealed by HSC-selective CAF depletion. In patients, a high panCAF signature is associated with decreased survival and increased recurrence. Single-cell RNA sequencing segregates CAF into inflammatory and growth factor-enriched (iCAF) and myofibroblastic (myCAF) subpopulations, displaying distinct ligand-receptor interactions. myCAF-expressed hyaluronan synthase 2, but not type I collagen, promotes ICC. iCAF-expressed hepatocyte growth factor enhances ICC growth via tumor-expressed MET, thus directly linking CAF to tumor cells. In summary, our data demonstrate promotion of desmoplastic ICC growth by therapeutically targetable CAF subtype-specific mediators, but not by type I collagen. Cancer-associated fibroblasts (CAF) are a poorly characterized cell population in the context of liver cancer. Our study investigates CAF functions in intrahepatic cholangiocarcinoma (ICC), a highly desmoplastic liver tumor. Genetic tracing, single-cell RNA-sequencing and ligand-receptor analyses uncovered hepatic stellate cells (HSC) as the main source of CAF, and HSC-derived CAF as dominant population interacting with tumor cells. In mice, CAF promotes ICC progression, as revealed by HSC-selective CAF depletion. In patients, a high panCAF signature is associated with decreased survival and increased recurrence. Single-cell RNA-sequencing segregates CAF into inflammatory and growth factor-enriched (iCAF) and myofibroblastic (myCAF) subpopulations, displaying distinct ligand-receptor interactions. myCAF-expressed hyaluronan synthase 2 but not type I collagen, promotes ICC. iCAF-expressed HGF enhances ICC growth via tumor-expressed MET, thus directly linking CAF to tumor cells. In summary, our data demonstrate promotion of desmoplastic ICC growth by therapeutically targetable CAF subtype-specific mediators, but not by type I collagen. Intrahepatic cholangiocarcinoma (ICC) is an extraordinarily stiff liver tumor due to abundant scar-forming cancer-associated fibroblasts (CAF). Here, Affo et al. determine origin and functions of CAF, and uncover distinct CAF subsets, promoting ICC growth via different therapeutically targetable mediators. Thus, CAF and their mediators may serve as therapeutic targets for ICC. |
| Author | Wen, Wen Riener, Marc-Oliver Remotti, Helen E. Ravichandra, Aashreya Schwabe, Robert F. Sims, Peter Worley, Jeremy Kalluri, Raghu Sia, Daniela Califano, Andrea Gaublomme, Jellert Seki, Ekihiro Wells, Rebecca G. Nair, Ajay Decker, Aubrianna Matsuda, Michitaka Arpaia, Nicholas Affo, Silvia Caviglia, Jorge Matias Yin, Deqi Zender, Lars Stockwell, Brent R. Savage, Thomas Chin, LiKang Llovet, Josep M. Yu, Lexing Chen, Xin Bhattacharjee, Sonakshi Brundu, Francesco Mack, Matthias Weber, Achim Song, Xinhua Michalopoulos, George K. Filliol, Aveline Leblond, Anne-Laure Rabadan, Raul Saito, Yoshinobu |
| AuthorAffiliation | 1 Department of Medicine, Columbia University, New York, 10032, NY, USA 22 Department of Biochemistry & Molecular Biophysics, Columbia University, New York, 10032, NY, USA 8 Department of Nephrology, University Hospital Regensburg, 93053, Regensburg, Germany 11 iFIT Cluster of Excellence EXC 2180, University of Tuebingen, 72076, Tuebingen, Germany 13 Department of Pathology & Cell Biology, Columbia University, New York, 10032, NY, USA 20 Department of Pathology, University of Pittsburgh, Pittsburgh, 15213, PA, USA 19 Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain 5 Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, 94158, CA, USA 12 Herbert Irving Comprehensive Cancer Center, Columbia University, New York, 10032, NY, USA 21 Department of Biomedical Informatics, Columbia University, New York, 10032, NY, USA 18 Mount Sinai Liver Cancer Program, Divisions of Liver Diseases, Tisch Cancer Institute, Icahn School of Med |
| AuthorAffiliation_xml | – name: 3 Department of Medicine, Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, 90024, CA, USA – name: 21 Department of Biomedical Informatics, Columbia University, New York, 10032, NY, USA – name: 22 Department of Biochemistry & Molecular Biophysics, Columbia University, New York, 10032, NY, USA – name: 19 Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain – name: 15 Department for Pathology and Molecular Pathology, Zürich University Hospital, 8091, Zürich, Switzerland – name: 13 Department of Pathology & Cell Biology, Columbia University, New York, 10032, NY, USA – name: 18 Mount Sinai Liver Cancer Program, Divisions of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA – name: 7 Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, 10032, NY, USA – name: 23 Institute of Human Nutrition, Columbia University, New York, 10032, NY, USA – name: 2 Department of Systems Biology, Columbia University Irving Medical Center, New York, 10032, NY, USA – name: 1 Department of Medicine, Columbia University, New York, 10032, NY, USA – name: 14 Department of Systems Biology, Columbia University, New York, 10032, NY, USA – name: 20 Department of Pathology, University of Pittsburgh, Pittsburgh, 15213, PA, USA – name: 17 Liver Cancer Translational Research Laboratory, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Universitat de Barcelona, 08036, Barcelona, Spain – name: 11 iFIT Cluster of Excellence EXC 2180, University of Tuebingen, 72076, Tuebingen, Germany – name: 12 Herbert Irving Comprehensive Cancer Center, Columbia University, New York, 10032, NY, USA – name: 6 Department of Biological Sciences, Columbia University, New York, 10027, NY, USA – name: 16 Department of Chemistry, Columbia University, New York, 10027, NY, USA – name: 4 Department of Medicine, Penn Physical Sciences in Oncology Center PSOC@Penn, University of Pennsylvania, Philadelphia, PA 19104, USA – name: 5 Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, 94158, CA, USA – name: 8 Department of Nephrology, University Hospital Regensburg, 93053, Regensburg, Germany – name: 24 Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA – name: 10 German Cancer Research Consortium (DKTK), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany – name: 9 Department of Medical Oncology and Pneumology, University Hospital Tuebingen, 72076, Tuebingen, Germany |
| Author_xml | – sequence: 1 givenname: Silvia surname: Affo fullname: Affo, Silvia organization: Department of Medicine, Columbia University, New York, NY 10032, USA – sequence: 2 givenname: Ajay orcidid: 0000-0003-4521-5614 surname: Nair fullname: Nair, Ajay organization: Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA – sequence: 3 givenname: Francesco orcidid: 0000-0003-2133-1426 surname: Brundu fullname: Brundu, Francesco organization: Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA – sequence: 4 givenname: Aashreya orcidid: 0000-0001-5785-8524 surname: Ravichandra fullname: Ravichandra, Aashreya organization: Department of Medicine, Columbia University, New York, NY 10032, USA – sequence: 5 givenname: Sonakshi surname: Bhattacharjee fullname: Bhattacharjee, Sonakshi organization: Department of Medicine, Columbia University, New York, NY 10032, USA – sequence: 6 givenname: Michitaka surname: Matsuda fullname: Matsuda, Michitaka organization: Department of Medicine, Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA 90024, USA – sequence: 7 givenname: LiKang surname: Chin fullname: Chin, LiKang organization: Department of Medicine, Penn Physical Sciences in Oncology Center PSOC@Penn, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 8 givenname: Aveline surname: Filliol fullname: Filliol, Aveline organization: Department of Medicine, Columbia University, New York, NY 10032, USA – sequence: 9 givenname: Wen orcidid: 0000-0002-7835-922X surname: Wen fullname: Wen, Wen organization: Department of Medicine, Columbia University, New York, NY 10032, USA – sequence: 10 givenname: Xinhua surname: Song fullname: Song, Xinhua organization: Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA 94158, USA – sequence: 11 givenname: Aubrianna orcidid: 0000-0002-0646-1815 surname: Decker fullname: Decker, Aubrianna organization: Department of Biological Sciences, Columbia University, New York, NY 10027, USA – sequence: 12 givenname: Jeremy surname: Worley fullname: Worley, Jeremy organization: Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA – sequence: 13 givenname: Jorge Matias surname: Caviglia fullname: Caviglia, Jorge Matias organization: Department of Medicine, Columbia University, New York, NY 10032, USA – sequence: 14 givenname: Lexing surname: Yu fullname: Yu, Lexing organization: Department of Medicine, Columbia University, New York, NY 10032, USA – sequence: 15 givenname: Deqi orcidid: 0000-0002-0022-3269 surname: Yin fullname: Yin, Deqi organization: Department of Medicine, Columbia University, New York, NY 10032, USA – sequence: 16 givenname: Yoshinobu orcidid: 0000-0002-0624-0449 surname: Saito fullname: Saito, Yoshinobu organization: Department of Medicine, Columbia University, New York, NY 10032, USA – sequence: 17 givenname: Thomas orcidid: 0000-0002-6618-2973 surname: Savage fullname: Savage, Thomas organization: Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA – sequence: 18 givenname: Rebecca G. orcidid: 0000-0002-6988-4102 surname: Wells fullname: Wells, Rebecca G. organization: Department of Medicine, Penn Physical Sciences in Oncology Center PSOC@Penn, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 19 givenname: Matthias surname: Mack fullname: Mack, Matthias organization: Department of Nephrology, University Hospital Regensburg, 93053 Regensburg, Germany – sequence: 20 givenname: Lars surname: Zender fullname: Zender, Lars organization: Department of Medical Oncology and Pneumology, University Hospital Tuebingen, 72076 Tuebingen, Germany – sequence: 21 givenname: Nicholas orcidid: 0000-0002-0657-0528 surname: Arpaia fullname: Arpaia, Nicholas organization: Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA – sequence: 22 givenname: Helen E. surname: Remotti fullname: Remotti, Helen E. organization: Department of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA – sequence: 23 givenname: Raul surname: Rabadan fullname: Rabadan, Raul organization: Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA – sequence: 24 givenname: Peter surname: Sims fullname: Sims, Peter organization: Department of Systems Biology, Columbia University, New York, NY 10032, USA – sequence: 25 givenname: Anne-Laure surname: Leblond fullname: Leblond, Anne-Laure organization: Department for Pathology and Molecular Pathology, Zürich University Hospital, 8091 Zürich, Switzerland – sequence: 26 givenname: Achim orcidid: 0000-0003-0073-3637 surname: Weber fullname: Weber, Achim organization: Department for Pathology and Molecular Pathology, Zürich University Hospital, 8091 Zürich, Switzerland – sequence: 27 givenname: Marc-Oliver surname: Riener fullname: Riener, Marc-Oliver organization: Department for Pathology and Molecular Pathology, Zürich University Hospital, 8091 Zürich, Switzerland – sequence: 28 givenname: Brent R. surname: Stockwell fullname: Stockwell, Brent R. organization: Department of Biological Sciences, Columbia University, New York, NY 10027, USA – sequence: 29 givenname: Jellert surname: Gaublomme fullname: Gaublomme, Jellert organization: Department of Biological Sciences, Columbia University, New York, NY 10027, USA – sequence: 30 givenname: Josep M. surname: Llovet fullname: Llovet, Josep M. organization: Liver Cancer Translational Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Universitat de Barcelona, 08036 Barcelona, Spain – sequence: 31 givenname: Raghu surname: Kalluri fullname: Kalluri, Raghu organization: Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA – sequence: 32 givenname: George K. orcidid: 0000-0001-9922-6920 surname: Michalopoulos fullname: Michalopoulos, George K. organization: Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA – sequence: 33 givenname: Ekihiro orcidid: 0000-0002-9472-6085 surname: Seki fullname: Seki, Ekihiro organization: Department of Medicine, Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA 90024, USA – sequence: 34 givenname: Daniela surname: Sia fullname: Sia, Daniela organization: Mount Sinai Liver Cancer Program, Divisions of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA – sequence: 35 givenname: Xin surname: Chen fullname: Chen, Xin organization: Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA 94158, USA – sequence: 36 givenname: Andrea orcidid: 0000-0003-4742-3679 surname: Califano fullname: Califano, Andrea organization: Department of Medicine, Columbia University, New York, NY 10032, USA – sequence: 37 givenname: Robert F. surname: Schwabe fullname: Schwabe, Robert F. email: rfs2102@cumc.columbia.edu organization: Department of Medicine, Columbia University, New York, NY 10032, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33930309$$D View this record in MEDLINE/PubMed |
| BookMark | eNpVkVtr3DAQhUVJaS7tLygUP-bFri62VnpIIIQ2LQTah7wWMZLGu1psaSPZW_Lv682N9GkG5swZ5nyn5CimiIR8ZrRhlMmv28Y5HIaGU84aKhrK-DtywtRK1UIqebT0nehqyag6JqelbOmyxVb6AzkWQgsqqD4hf37nNKYppFilvnKbNEBch-QguxDTCNU6p7_TprIPlQ97zAUrB9FhrqGU5AJM6Ks-2JzsAGWqymx3aTcPcLAsH8n7HoaCn57rGbn7_u3u-kd9--vm5_XVbY2tYFPt21ZR1TlQSlgrJXoFXHsJzlNNW94Co3alFXLeS0RsV9ZC63RvlbK9F2fk8sl2N9sRvcM4ZRjMLocR8oNJEMz_kxg2Zp32RvGWcdEtBufPBjndz1gmM4ZyCBciprkY3nGqpNBML9Ivb2-9HnmJdBFcPAlweXgfMJviAi6R-ZDRTcanYBg1B4Rmax4RmgNCQ4VZEIp_1naU8g |
| ContentType | Journal Article |
| Copyright | 2021 Elsevier Inc. Copyright © 2021 Elsevier Inc. All rights reserved. |
| Copyright_xml | – notice: 2021 Elsevier Inc. – notice: Copyright © 2021 Elsevier Inc. All rights reserved. |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 5PM |
| DOI | 10.1016/j.ccell.2021.03.012 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1878-3686 |
| EndPage | 882.e11 |
| ExternalDocumentID | PMC8241235 33930309 S1535610821001707 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NCI NIH HHS grantid: U01 CA217858 – fundername: NCI NIH HHS grantid: R35 CA197745 – fundername: NCI NIH HHS grantid: U54 CA193417 – fundername: NIDDK NIH HHS grantid: R03 DK101863 – fundername: NCI NIH HHS grantid: R35 CA209896 – fundername: NIDDK NIH HHS grantid: R01 DK085252 – fundername: NIH HHS grantid: S10 OD021764 – fundername: NCI NIH HHS grantid: R01 CA190606 – fundername: NINDS NIH HHS grantid: R61 NS109407 – fundername: NIH HHS grantid: S10 OD012351 |
| GroupedDBID | --- --K 0R~ 1~5 29B 2WC 4.4 457 4G. 53G 5GY 62- 6J9 7-5 AACTN AAEDT AAEDW AAFTH AAIAV AAKRW AAKUH AALRI AAUCE AAVLU AAXUO ABJNI ABMAC ABMWF ABVKL ACGFO ACGFS ADBBV ADEZE ADJPV AEFWE AENEX AEXQZ AFTJW AGKMS AITUG ALKID ALMA_UNASSIGNED_HOLDINGS AMRAJ ASPBG AVWKF AZFZN BAWUL CS3 DIK DU5 E3Z EBS F5P FCP FDB FEDTE FIRID HVGLF IH2 IHE IXB J1W JIG M3Z M41 O-L O9- OK1 P2P RCE ROL RPZ SES SSZ TR2 UDS WQ6 ZA5 AAFWJ AAMRU AAYWO ABDGV ACVFH ADCNI ADVLN AEUPX AFPUW AGCQF AIGII AKAPO AKBMS AKRWK AKYEP APXCP CGR CUY CVF ECM EFKBS EIF NPM 7X8 5PM |
| ID | FETCH-LOGICAL-e431t-d448085ca883bb66ed8a29d6acd090424a10b798e22f6eee47bba4c9fb88bfd3 |
| IEDL.DBID | IXB |
| ISSN | 1535-6108 1878-3686 |
| IngestDate | Thu Aug 21 13:45:51 EDT 2025 Tue Aug 05 10:00:15 EDT 2025 Mon Jul 21 06:00:28 EDT 2025 Fri Feb 23 02:43:40 EST 2024 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 6 |
| Keywords | single cell immune mechanosensitive CellPhoneDB HGF YAP KRAS tumor microenvironment stiffness cholangiocarcinoma |
| Language | English |
| License | Copyright © 2021 Elsevier Inc. All rights reserved. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-e431t-d448085ca883bb66ed8a29d6acd090424a10b798e22f6eee47bba4c9fb88bfd3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceptualization, R.F.S and S.A.; Methodology, R.F.S., S.A., X.C., R.G.W., A.N., F.B., D.S.; Experimentation, S.A., A.N, F.B., A.R., S.B., T.S., M.M., L.C., A.F., W.W., Y.S., J.W., D.Y., X.S., A.D., J.M.C., L.Z., H.E.R., A.L.L., D.S.; Writing, R.F.S and S.A.; Funding Acquisition, R.F.S., X.C. and S.A.; Resources, R.F.S., N.A., A.M., M.O.R., B.R.S., J.G., G.K.M., L.S., J.M.L., D.S., E.S., R.R., P.S., X.C., and A.C.; Supervision, R.F.S. AUTHOR CONTRIBUTIONS |
| ORCID | 0000-0002-0657-0528 0000-0003-4521-5614 0000-0002-9472-6085 0000-0003-4742-3679 0000-0002-6988-4102 0000-0002-0624-0449 0000-0002-0022-3269 0000-0003-0073-3637 0000-0003-2133-1426 0000-0002-6618-2973 0000-0002-7835-922X 0000-0001-5785-8524 0000-0001-9922-6920 0000-0002-0646-1815 |
| OpenAccessLink | http://www.cell.com/article/S1535610821001707/pdf |
| PMID | 33930309 |
| PQID | 2520863919 |
| PQPubID | 23479 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_8241235 proquest_miscellaneous_2520863919 pubmed_primary_33930309 elsevier_sciencedirect_doi_10_1016_j_ccell_2021_03_012 |
| PublicationCentury | 2000 |
| PublicationDate | 2021-06-14 |
| PublicationDateYYYYMMDD | 2021-06-14 |
| PublicationDate_xml | – month: 06 year: 2021 text: 2021-06-14 day: 14 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Cancer cell |
| PublicationTitleAlternate | Cancer Cell |
| PublicationYear | 2021 |
| Publisher | Elsevier Inc |
| Publisher_xml | – name: Elsevier Inc |
| References | Reich, Liefeld, Gould, Lerner, Tamayo, Mesirov (bib54) 2006; 38 Banales, Marin, Lamarca, Rodrigues, Khan, Roberts, Cardinale, Carpino, Andersen, Braconi (bib4) 2020; 17 Rhim, Oberstein, Thomas, Mirek, Palermo, Sastra, Dekleva, Saunders, Becerra, Tattersall (bib56) 2014; 25 Liotta (bib34) 1986; 46 Ohlund, Handly-Santana, Biffi, Elyada, Almeida, Ponz-Sarvise, Corbo, Oni, Hearn, Lee (bib47) 2017; 214 Hosein, Huang, Wang, Parmar, Du, Huang, Maitra, Olson, Verma, Brekken (bib27) 2019; 5 Marti, Stein, Blumer, Abraham, Dill, Pikiolek, Orsini, Jurisic, Megel, Makowska (bib37) 2015; 62 Vento-Tormo, Efremova, Botting, Turco, Vento-Tormo, Meyer, Park, Stephenson, Polanski, Goncalves (bib70) 2018; 563 Friedman, Levi-Galibov, David, Bornstein, Giladi, Dadiani, Mayo, Halperin, Pevsner-Fischer, Lavon (bib25) 2020; 1 Mederacke, Dapito, Affo, Uchinami, Schwabe (bib42) 2015; 10 Friedman (bib24) 2008; 88 Riener, Vogetseder, Pestalozzi, Clavien, Probst-Hensch, Kristiansen, Jochum (bib57) 2010; 41 Egeblad, Rasch, Weaver (bib19) 2010; 22 Seehawer, Heinzmann, D'Artista, Harbig, Roux, Hoenicke, Dang, Klotz, Robinson, Dore (bib62) 2018; 562 Clements, Eliahoo, Kim, Taylor-Robinson, Khan (bib15) 2020; 72 Senoo, Mezaki, Fujiwara (bib63) 2017; 92 Catenacci, Junttila, Karrison, Bahary, Horiba, Nattam, Marsh, Wallace, Kozloff, Rajdev (bib11) 2015; 33 Sia, Hoshida, Villanueva, Roayaie, Ferrer, Tabak, Peix, Sole, Tovar, Alsinet (bib64) 2013; 144 Chowdhury, Castro, Coker, Hinchliffe, Arpaia, Danino (bib14) 2019; 25 Affo, Yu, Schwabe (bib1) 2017; 12 Chen, Song (bib13) 2019; 18 Huh, Factor, Sanchez, Uchida, Conner, Thorgeirsson (bib28) 2004; 101 Sirica (bib65) 2011; 9 Zhang, Yang, Wan, Wang, Wang, Ge, Liu, Hao, Zhang, Shi (bib74) 2020; 73 Cyphert, Trempus, Garantziotis (bib18) 2015; 2015 Tian, Azpurua, Hine, Vaidya, Myakishev-Rempel, Ablaeva, Mao, Nevo, Gorbunova, Seluanov (bib68) 2013; 499 Rizvi, Khan, Hallemeier, Kelley, Gores (bib59) 2018; 15 Biffi, Tuveson (bib8) 2020; 101 Buchtler, Grill, Hofmarksrichter, Stockert, Schiechl-Brachner, Rodriguez Gomez, Neumayer, Schmidbauer, Talke, Klinkhammer (bib10) 2018; 29 Mertens, Fingas, Christensen, Smoot, Bronk, Werneburg, Gustafson, Dietz, Roberts, Sirica, Gores (bib43) 2013; 73 Ilicic, Kim, Kolodziejczyk, Bagger, McCarthy, Marioni, Teichmann (bib29) 2016; 17 Ramanathan, McDonough, Philip, Hingorani, Lacy, Kortmansky, Thumar, Chiorean, Shields, Behl (bib52) 2019; 37 Lun, Bach, Marioni (bib35) 2016; 17 Pradere, Kluwe, De Minicis, Jiao, Gwak, Dapito, Jang, Guenther, Mederacke, Friedman (bib50) 2013; 58 Blondel, Guillaume, Lambiotte, Lefebvre (bib9) 2008; 6 Barbazan, Matic Vignjevic (bib6) 2019; 56 Levental, Yu, Kass, Lakins, Egeblad, Erler, Fong, Csiszar, Giaccia, Weninger (bib33) 2009; 139 Erez, Truitt, Olson, Arron, Hanahan (bib21) 2010; 17 Mederacke, Hsu, Troeger, Huebener, Mu, Dapito, Pradere, Schwabe (bib41) 2013; 4 Fan, Malato, Calvisi, Naqvi, Razumilava, Ribback, Gores, Dombrowski, Evert, Chen, Willenbring (bib22) 2012; 122 Toole (bib69) 2004; 4 Rousseeuw (bib60) 1987; 20 Kalluri (bib30) 2016; 16 Caviglia, Yan, Jang, Gwak, Affo, Yu, Olinga, Friedman, Chen, Schwabe (bib12) 2018; 67 Wang, Dong, Xu, Song, Zhang, Qiao, Che, Gordan, Hu, Liu (bib71) 2018; 37 Barbie, Tamayo, Boehm, Kim, Moody, Dunn, Schinzel, Sandy, Meylan, Scholl (bib7) 2009; 462 Kononen, Bubendorf, Kallioniemi, Barlund, Schraml, Leighton, Torhorst, Mihatsch, Sauter, Kallioniemi (bib31) 1998; 4 Northey, Przybyla, Weaver (bib46) 2017; 7 Stuart, Butler, Hoffman, Hafemeister, Papalexi, Mauck, Hao, Stoeckius, Smibert, Satija (bib66) 2019; 177 McCarthy, El-Ashry, Turley (bib39) 2018; 6 Matsumoto, Li, Jakuba, Sugiyama, Sayo, Okuno, Dealy, Toole, Takeda, Yamaguchi, Kosher (bib38) 2009; 136 Bankhead, Loughrey, Fernandez, Dombrowski, McArt, Dunne, McQuaid, Gray, Murray, Coleman (bib5) 2017; 7 Krempen, Grotkopp, Hall, Bache, Gillan, Rippe, Brenner, Breindl (bib32) 1999; 8 Aparicio, Bordyuh, Blumberg, Rabadan (bib3) 2020; 1 Comoglio, Trusolino, Boccaccio (bib16) 2018; 18 Mu, Pradere, Affo, Dapito, Friedman, Lefkovitch, Schwabe (bib45) 2016; 150 Provenzano, Cuevas, Chang, Goel, Von Hoff, Hingorani (bib51) 2012; 21 Costa, Kieffer, Scholer-Dahirel, Pelon, Bourachot, Cardon, Sirven, Magagna, Fuhrmann, Bernard (bib17) 2018; 33 Hanahan, Coussens (bib26) 2012; 21 Franzén, Gan, Björkegren (bib23) 2019; 2019 Wang, Wang, Peters, Ding, Ribback, Utpatel, Cigliano, Dombrowski, Xu, Chen (bib72) 2019; 71 Sahai, Astsaturov, Cukierman, DeNardo, Egeblad, Evans, Fearon, Greten, Hingorani, Hunter (bib61) 2020; 20 Reimand, Isserlin, Voisin, Kucera, Tannus-Lopes, Rostamianfar, Wadi, Meyer, Wong, Xu (bib55) 2019; 14 Elyada, Bolisetty, Laise, Flynn, Courtois, Burkhart, Teinor, Belleau, Biffi, Lucito (bib20) 2019; 9 Michalopoulos, DeFrances (bib44) 1997; 276 Ozdemir, Pentcheva-Hoang, Carstens, Zheng, Wu, Simpson, Laklai, Sugimoto, Kahlert, Novitskiy (bib48) 2014; 25 Raudvere, Kolberg, Kuzmin, Arak, Adler, Peterson, Vilo (bib53) 2019; 47 Rizvi, Fischbach, Bronk, Hirsova, Krishnan, Dhanasekaran, Smadbeck, Smoot, Vasmatzis, Gores (bib58) 2018; 9 Su, Chen, Yao, Liu, Yu, Lao, Wang, Luo, Xing, Chen (bib67) 2018; 172 Yang, Noureddin, Liu, Ohashi, Kim, Ramnath, Powell, Sweet, Roh, Hsin (bib73) 2019; 11 Algul, Treiber, Lesina, Nakhai, Saur, Geisler, Pfeifer, Paxian, Schmid (bib2) 2007; 117 Phaneuf, Moscioni, LeClair, Raper, Wilson (bib49) 2004; 23 McInnes, Healy (bib40) 2018 Ma, Hernandez, Zhao, Mehta, Tran, Kelly, Rae, Hernandez, Davis, Martin (bib36) 2019; 36 34129825 - Cancer Cell. 2021 Jun 14;39(6):883 |
| References_xml | – volume: 5 start-page: e129212 year: 2019 ident: bib27 article-title: Cellular heterogeneity during mouse pancreatic ductal adenocarcinoma progression at single-cell resolution publication-title: JCI Insight – volume: 25 start-page: 719 year: 2014 end-page: 734 ident: bib48 article-title: Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival publication-title: Cancer Cell – volume: 4 start-page: 2823 year: 2013 ident: bib41 article-title: Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology publication-title: Nat. Commun. – volume: 72 start-page: 95 year: 2020 end-page: 103 ident: bib15 article-title: Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a systematic review and meta-analysis publication-title: J. Hepatol. – volume: 36 start-page: 418 year: 2019 end-page: 430.e16 ident: bib36 article-title: Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer publication-title: Cancer Cell – volume: 20 start-page: 174 year: 2020 end-page: 186 ident: bib61 article-title: A framework for advancing our understanding of cancer-associated fibroblasts publication-title: Nat. Rev. Cancer – volume: 122 start-page: 2911 year: 2012 end-page: 2915 ident: bib22 article-title: Cholangiocarcinomas can originate from hepatocytes in mice publication-title: J. Clin. Invest. – volume: 67 start-page: 2414 year: 2018 end-page: 2429 ident: bib12 article-title: MicroRNA-21 and Dicer are dispensable for hepatic stellate cell activation and the development of liver fibrosis publication-title: Hepatology – volume: 101 start-page: 147 year: 2020 end-page: 176 ident: bib8 article-title: Diversity and biology of cancer-associated fibroblasts publication-title: Physiol. Rev. – volume: 6 start-page: 48 year: 2018 ident: bib39 article-title: Hyaluronan, cancer-associated fibroblasts and the tumor microenvironment in malignant progression publication-title: Front. Cell Dev. Biol. – volume: 18 start-page: 99 year: 2019 end-page: 115 ident: bib13 article-title: Turning foes to friends: targeting cancer-associated fibroblasts publication-title: Nat. Rev. Drug Discov. – volume: 139 start-page: 891 year: 2009 end-page: 906 ident: bib33 article-title: Matrix crosslinking forces tumor progression by enhancing integrin signaling publication-title: Cell – volume: 73 start-page: 897 year: 2013 end-page: 907 ident: bib43 article-title: Therapeutic effects of deleting cancer-associated fibroblasts in cholangiocarcinoma publication-title: Cancer Res. – volume: 46 start-page: 1 year: 1986 end-page: 7 ident: bib34 article-title: Tumor invasion and metastases—role of the extracellular matrix: Rhoads Memorial Award lecture publication-title: Cancer Res. – volume: 41 start-page: 1558 year: 2010 end-page: 1565 ident: bib57 article-title: Cell adhesion molecules P-cadherin and CD24 are markers for carcinoma and dysplasia in the biliary tract publication-title: Hum. Pathol. – volume: 21 start-page: 418 year: 2012 end-page: 429 ident: bib51 article-title: Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma publication-title: Cancer Cell – volume: 172 start-page: 841 year: 2018 end-page: 856.e16 ident: bib67 article-title: CD10(+)GPR77(+) cancer-associated fibroblasts promote cancer formation and chemoresistance by sustaining cancer stemness publication-title: Cell – volume: 499 start-page: 346 year: 2013 end-page: 349 ident: bib68 article-title: High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat publication-title: Nature – volume: 17 start-page: 75 year: 2016 ident: bib35 article-title: Pooling across cells to normalize single-cell RNA sequencing data with many zero counts publication-title: Genome Biol. – volume: 37 start-page: 1062 year: 2019 end-page: 1069 ident: bib52 article-title: Phase IB/II randomized study of FOLFIRINOX plus pegylated recombinant human hyaluronidase versus FOLFIRINOX alone in patients with metastatic pancreatic adenocarcinoma: swog S1313 publication-title: J. Clin. Oncol. – volume: 25 start-page: 1057 year: 2019 end-page: 1063 ident: bib14 article-title: Programmable bacteria induce durable tumor regression and systemic antitumor immunity publication-title: Nat. Med. – volume: 20 start-page: 53 year: 1987 end-page: 65 ident: bib60 article-title: Silhouettes: a graphical aid to the interpretation and validation of cluster analysis publication-title: J. Comput. Appl. Math. – volume: 4 start-page: 528 year: 2004 end-page: 539 ident: bib69 article-title: Hyaluronan: from extracellular glue to pericellular cue publication-title: Nat. Rev. Cancer – volume: 214 start-page: 579 year: 2017 end-page: 596 ident: bib47 article-title: Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer publication-title: J. Exp. Med. – volume: 71 start-page: 742 year: 2019 end-page: 752 ident: bib72 article-title: Loss of Fbxw7 synergizes with activated Akt signaling to promote c-Myc dependent cholangiocarcinogenesis publication-title: J. Hepatol. – volume: 101 start-page: 4477 year: 2004 end-page: 4482 ident: bib28 article-title: Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair publication-title: Proc. Natl. Acad. Sci. U S A – volume: 18 start-page: 341 year: 2018 end-page: 358 ident: bib16 article-title: Known and novel roles of the MET oncogene in cancer: a coherent approach to targeted therapy publication-title: Nat. Rev. Cancer – volume: 144 start-page: 829 year: 2013 end-page: 840 ident: bib64 article-title: Integrative molecular analysis of intrahepatic cholangiocarcinoma reveals 2 classes that have different outcomes publication-title: Gastroenterology – volume: 92 start-page: 387 year: 2017 end-page: 455 ident: bib63 article-title: The stellate cell system (vitamin A-storing cell system) publication-title: Anat. Sci. Int. – volume: 56 start-page: 71 year: 2019 end-page: 79 ident: bib6 article-title: Cancer associated fibroblasts: is the force the path to the dark side? publication-title: Curr. Opin. Cell Biol. – volume: 62 start-page: 1497 year: 2015 end-page: 1510 ident: bib37 article-title: YAP promotes proliferation, chemoresistance, and angiogenesis in human cholangiocarcinoma through TEAD transcription factors publication-title: Hepatology – volume: 9 start-page: 5892 year: 2018 end-page: 5905 ident: bib58 article-title: YAP-associated chromosomal instability and cholangiocarcinoma in mice publication-title: Oncotarget – volume: 38 start-page: 500 year: 2006 end-page: 501 ident: bib54 article-title: GenePattern 2.0 publication-title: Nat. Genet. – volume: 22 start-page: 697 year: 2010 end-page: 706 ident: bib19 article-title: Dynamic interplay between the collagen scaffold and tumor evolution publication-title: Curr. Opin. Cell Biol. – volume: 136 start-page: 2825 year: 2009 end-page: 2835 ident: bib38 article-title: Conditional inactivation of Has2 reveals a crucial role for hyaluronan in skeletal growth, patterning, chondrocyte maturation and joint formation in the developing limb publication-title: Development – volume: 21 start-page: 309 year: 2012 end-page: 322 ident: bib26 article-title: Accessories to the crime: functions of cells recruited to the tumor microenvironment publication-title: Cancer Cell – volume: 562 start-page: 69 year: 2018 end-page: 75 ident: bib62 article-title: Necroptosis microenvironment directs lineage commitment in liver cancer publication-title: Nature – volume: 2019 year: 2019 ident: bib23 article-title: PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data publication-title: Database – volume: 12 start-page: 153 year: 2017 end-page: 186 ident: bib1 article-title: The role of cancer-associated fibroblasts and fibrosis in liver cancer publication-title: Annu. Rev. Pathol. – volume: 88 start-page: 125 year: 2008 end-page: 172 ident: bib24 article-title: Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver publication-title: Physiol. Rev. – volume: 33 start-page: 463 year: 2018 end-page: 479.e10 ident: bib17 article-title: Fibroblast heterogeneity and immunosuppressive environment in human breast cancer publication-title: Cancer Cell – volume: 7 start-page: 1224 year: 2017 end-page: 1237 ident: bib46 article-title: Tissue force programs cell fate and tumor aggression publication-title: Cancer Discov. – volume: 17 start-page: 557 year: 2020 end-page: 588 ident: bib4 article-title: Cholangiocarcinoma 2020: the next horizon in mechanisms and management publication-title: Nat. Rev. Gastroenterol. Hepatol. – volume: 9 start-page: 1102 year: 2019 end-page: 1123 ident: bib20 article-title: Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts publication-title: Cancer Discov. – volume: 150 start-page: 720 year: 2016 end-page: 733 ident: bib45 article-title: Epithelial transforming growth factor-beta signaling does not contribute to liver fibrosis but protects mice from cholangiocarcinoma publication-title: Gastroenterology – volume: 25 start-page: 735 year: 2014 end-page: 747 ident: bib56 article-title: Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma publication-title: Cancer Cell – volume: 1 start-page: 100035 year: 2020 ident: bib3 article-title: A random matrix theory approach to Denoise single-cell data publication-title: Patterns (N Y) – volume: 23 start-page: 592 year: 2004 end-page: 603 ident: bib49 article-title: Generation of a mouse expressing a conditional knockout of the hepatocyte growth factor gene: demonstration of impaired liver regeneration publication-title: DNA Cell Biol. – volume: 58 start-page: 1461 year: 2013 end-page: 1473 ident: bib50 article-title: Hepatic macrophages but not dendritic cells contribute to liver fibrosis by promoting the survival of activated hepatic stellate cells in mice publication-title: Hepatology – volume: 117 start-page: 1490 year: 2007 end-page: 1501 ident: bib2 article-title: Pancreas-specific RelA/p65 truncation increases susceptibility of acini to inflammation-associated cell death following cerulein pancreatitis publication-title: J. Clin. Invest. – volume: 17 start-page: 135 year: 2010 end-page: 147 ident: bib21 article-title: Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner publication-title: Cancer Cell – volume: 6 start-page: 10008 year: 2008 ident: bib9 article-title: Fast unfolding of communities in large networks publication-title: J. Stat. Mech. Theor. Exp – volume: 9 start-page: 44 year: 2011 end-page: 54 ident: bib65 article-title: The role of cancer-associated myofibroblasts in intrahepatic cholangiocarcinoma publication-title: Nat. Rev. Gastroenterol. Hepatol. – volume: 7 start-page: 16878 year: 2017 ident: bib5 article-title: QuPath: open source software for digital pathology image analysis publication-title: Sci. Rep. – volume: 11 start-page: eaat9284 year: 2019 ident: bib73 article-title: Hyaluronan synthase 2-mediated hyaluronan production mediates Notch1 activation and liver fibrosis publication-title: Sci. Transl. Med. – volume: 2015 start-page: 563818 year: 2015 ident: bib18 article-title: Size matters: molecular weight specificity of hyaluronan effects in cell biology publication-title: Int. J. Cell Biol. – volume: 563 start-page: 347 year: 2018 end-page: 353 ident: bib70 article-title: Single-cell reconstruction of the early maternal-fetal interface in humans publication-title: Nature – volume: 4 start-page: 844 year: 1998 end-page: 847 ident: bib31 article-title: Tissue microarrays for high-throughput molecular profiling of tumor specimens publication-title: Nat. Med. – volume: 462 start-page: 108 year: 2009 end-page: 112 ident: bib7 article-title: Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1 publication-title: Nature – volume: 47 start-page: W191 year: 2019 end-page: W198 ident: bib53 article-title: g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update) publication-title: Nucleic Acids Res. – volume: 37 start-page: 3229 year: 2018 end-page: 3242 ident: bib71 article-title: Notch2 controls hepatocyte-derived cholangiocarcinoma formation in mice publication-title: Oncogene – volume: 1 start-page: 692 year: 2020 end-page: 708 ident: bib25 article-title: Cancer-associated fibroblast compositions change with breast cancer progression linking the ratio of S100A4+ and PDPN+ CAFs to clinical outcome publication-title: Nat. Cancer – volume: 16 start-page: 582 year: 2016 end-page: 598 ident: bib30 article-title: The biology and function of fibroblasts in cancer publication-title: Nat. Rev. Cancer – volume: 17 start-page: 29 year: 2016 ident: bib29 article-title: Classification of low quality cells from single-cell RNA-seq data publication-title: Genome Biol. – volume: 14 start-page: 482 year: 2019 end-page: 517 ident: bib55 article-title: Pathway enrichment analysis and visualization of omics data using g:Profiler, GSEA, Cytoscape and EnrichmentMap publication-title: Nat. Protoc. – volume: 177 start-page: 1888 year: 2019 end-page: 1902.e21 ident: bib66 article-title: Comprehensive integration of single-cell data publication-title: Cell – volume: 10 start-page: 305 year: 2015 end-page: 315 ident: bib42 article-title: High-yield and high-purity isolation of hepatic stellate cells from normal and fibrotic mouse livers publication-title: Nat. Protoc. – year: 2018 ident: bib40 article-title: UMAP: uniform manifold approximation and projection for dimension reduction publication-title: arXiv – volume: 276 start-page: 60 year: 1997 end-page: 66 ident: bib44 article-title: Liver regeneration publication-title: Science – volume: 29 start-page: 1859 year: 2018 end-page: 1873 ident: bib10 article-title: Cellular origin and functional relevance of collagen I production in the kidney publication-title: J. Am. Soc. Nephrol. – volume: 8 start-page: 151 year: 1999 end-page: 163 ident: bib32 article-title: Far upstream regulatory elements enhance position-independent and uterus-specific expression of the murine alpha1(I) collagen promoter in transgenic mice publication-title: Gene Expr. – volume: 15 start-page: 95 year: 2018 end-page: 111 ident: bib59 article-title: Cholangiocarcinoma - evolving concepts and therapeutic strategies publication-title: Nat. Rev. Clin. Oncol. – volume: 73 start-page: 1118 year: 2020 end-page: 1130 ident: bib74 article-title: Single cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma publication-title: J. Hepatol. – volume: 33 start-page: 4284 year: 2015 end-page: 4292 ident: bib11 article-title: Randomized phase ib/II study of gemcitabine plus placebo or vismodegib, a hedgehog pathway inhibitor, in patients with metastatic pancreatic cancer publication-title: J. Clin. Oncol. – reference: 34129825 - Cancer Cell. 2021 Jun 14;39(6):883 |
| SSID | ssj0016179 |
| Score | 2.6913657 |
| Snippet | Cancer-associated fibroblasts (CAF) are a poorly characterized cell population in the context of liver cancer. Our study investigates CAF functions in... |
| SourceID | pubmedcentral proquest pubmed elsevier |
| SourceType | Open Access Repository Aggregation Database Index Database Publisher |
| StartPage | 866 |
| SubjectTerms | Aged Animals Bile Duct Neoplasms - genetics Bile Duct Neoplasms - metabolism Bile Duct Neoplasms - pathology Bile Ducts, Intrahepatic - pathology Cancer-Associated Fibroblasts - metabolism Cancer-Associated Fibroblasts - pathology CellPhoneDB cholangiocarcinoma Cholangiocarcinoma - genetics Cholangiocarcinoma - metabolism Cholangiocarcinoma - pathology Collagen Type I - metabolism Female Hepatic Stellate Cells - cytology Hepatic Stellate Cells - pathology Hepatocyte Growth Factor - metabolism HGF Humans Hyaluronan Synthases - genetics Hyaluronan Synthases - metabolism Hyaluronic Acid - metabolism immune KRAS Male mechanosensitive Mice, Transgenic Middle Aged Proto-Oncogene Proteins c-met - metabolism single cell stiffness Tumor Microenvironment YAP |
| Title | Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations |
| URI | https://dx.doi.org/10.1016/j.ccell.2021.03.012 https://www.ncbi.nlm.nih.gov/pubmed/33930309 https://www.proquest.com/docview/2520863919 https://pubmed.ncbi.nlm.nih.gov/PMC8241235 |
| Volume | 39 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3NS-wwEA_iQbyIX--5fhHBa9ht0o_kqKKIoAgq7EVC0iS6D2yX3e7B_96ZtF1c381jmxzCzHTmN53fTAg5D6XzEIULZjNZslTylEnjDPMOO9EdL0LAiu79Q377kt6Ns_Eauep7YZBW2fn-1qdHb929GXbSHE4nk-ETfKsY_CVP4hAY7CgXqYxNfOPLZSUBIrRqZ6ZmDHf3k4cix6vEv-OQJPIkTjrFaym_haT_IedP5uS3UHSzTbY6DEkv2mPukDVf7ZKN-65KvkdeH1uOXV3ROtCYvVZvEwhaM1ivPwx9g9y7eaf2k7pIy_C0ROXPmOmU5R0NkEfXFrB1Q-cLO13e8zXfJ883189Xt6y7RoGBFpKGOcjAAFiVRkphbZ57Jw1XLjelGymsfJpkZAslPech996nhbUmLVWwUtrgxB-yXtWVPyA080EJA5gtL2JF1IrUGicAUVkLMEMOSN5LT68oUYN_1j2f7J-OYtcodj0SGsQ-IGe9rDWYNy6byteLueYZh6RLqEQNyN9W9nrazuHQQiiBFaIBKVa0styAo7NXV6rJexyhDTaJTcKHvz3wEdnEJ-SMJekxWW9mC38C6KSxp9H8vgD_ROeA |
| linkProvider | Elsevier |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9swDCa6Dth6KfZu9tSAXY3Ekh_SsStWpFtTDFgG5DIIkiW1GVA7SJxD__1I2Q6a7barqYPwUSI_mhQJ8ClUzqMXLhObyyrJJM8SaZxJvKOX6I6XIVBGd3ZVTH9mXxf54gDOhrcwVFbZ2_7Opkdr3X8Z92iOV8vl-AfeVXL-kqexCUz5AB4iGyhpfsPF4vMulYAuWnVNU_OElg-th2KRV0W_xzFK5GlsdUpzKe_5pH8559-lk_d80fkTOO5JJDvt9vkUDnz9DB7N-jT5c_j1vSuya2rWBBbD1_p6iV5rjfLm1rBrDL7bG2bvmIt1GZ5VpP11YnpteccCBtKNRXLdss3WrnaDvjYvYH7-ZX42Tfo5CgmqIW0ThyEYMqvKSCmsLQrvpOHKFaZyE0WpT5NObKmk5zwU3vustNZklQpWShuceAmHdVP7E2C5D0oYJG0IM6VErciscQIplbXIM-QIigE9vadFjQZaDwVlv3WEXRPseiI0wj6CjwPWGs83iU3tm-1G85xj1CVUqkbwqsNer7pGHFoIJShFNIJyTyu7BdQ7e19SL29iD208lPRK-PX_bvgDPJ7OZ5f68uLq2xs4IgkVkKXZWzhs11v_DqlKa9_Ho_gHp4Lqnw |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Promotion+of+cholangiocarcinoma+growth+by+diverse+cancer-associated+fibroblast+subpopulations&rft.jtitle=Cancer+cell&rft.au=Affo%2C+Silvia&rft.au=Nair%2C+Ajay&rft.au=Brundu%2C+Francesco&rft.au=Ravichandra%2C+Aashreya&rft.date=2021-06-14&rft.pub=Elsevier+Inc&rft.issn=1535-6108&rft.eissn=1878-3686&rft.volume=39&rft.issue=6&rft.spage=866&rft.epage=882.e11&rft_id=info:doi/10.1016%2Fj.ccell.2021.03.012&rft.externalDocID=S1535610821001707 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1535-6108&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1535-6108&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1535-6108&client=summon |