Characterization of Mutational Status, Spheroid Formation, and Drug Response of a New Genomically-Stable Human Ovarian Clear Cell Carcinoma Cell Line, 105C
Ovarian clear cell carcinoma (OCCC) is a rare subtype of gynecological cancer for which well-characterized and authenticated model systems are scarce. We provide an extensive characterization of '105C', a cell line generated from an adenocarcinoma of the clear cell histotype using targeted...
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| Published in | Cells (Basel, Switzerland) Vol. 9; no. 11; p. 2408 |
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| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
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03.11.2020
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| Abstract | Ovarian clear cell carcinoma (OCCC) is a rare subtype of gynecological cancer for which well-characterized and authenticated model systems are scarce. We provide an extensive characterization of '105C', a cell line generated from an adenocarcinoma of the clear cell histotype using targeted next-generation sequencing, cytogenetic microarrays, along with analyses of AKT/mTOR signaling. We report that that the 105C cell line is a bona fide OCCC cell line, carrying PIK3CA, PTEN, and ARID1A gene mutations, consistent with OCCC, yet maintain a stable genome as reflected by low copy number variation. Unlike KOC-7c, TOV-21G, and RMG-V OCCC lines also mutated for the above genes, the 105C cells do not carry mutations in mismatch repair genes. Importantly, we show that 105C cells exhibit greater resistance to mTOR inhibition and carboplatin treatment compared to 9 other OCCC cell lines in 3D spheroid cultures. This resistance may be attributed to 105C cells remaining dormant in suspension culture which surprisingly, contrasts with several other OCCC lines which continue to proliferate in long-term suspension culture. 105C cells survive xenotransplantation but do not proliferate and metastasize. Collectively, we show that the 105C OCCC cell line exhibits unique properties useful for the pre-clinical investigation of OCCC pathobiology. |
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| AbstractList | Ovarian clear cell carcinoma (OCCC) is a rare subtype of gynecological cancer for which well-characterized and authenticated model systems are scarce. We provide an extensive characterization of '105C', a cell line generated from an adenocarcinoma of the clear cell histotype using targeted next-generation sequencing, cytogenetic microarrays, along with analyses of AKT/mTOR signaling. We report that that the 105C cell line is a bona fide OCCC cell line, carrying PIK3CA, PTEN, and ARID1A gene mutations, consistent with OCCC, yet maintain a stable genome as reflected by low copy number variation. Unlike KOC-7c, TOV-21G, and RMG-V OCCC lines also mutated for the above genes, the 105C cells do not carry mutations in mismatch repair genes. Importantly, we show that 105C cells exhibit greater resistance to mTOR inhibition and carboplatin treatment compared to 9 other OCCC cell lines in 3D spheroid cultures. This resistance may be attributed to 105C cells remaining dormant in suspension culture which surprisingly, contrasts with several other OCCC lines which continue to proliferate in long-term suspension culture. 105C cells survive xenotransplantation but do not proliferate and metastasize. Collectively, we show that the 105C OCCC cell line exhibits unique properties useful for the pre-clinical investigation of OCCC pathobiology. |
| Audience | Academic |
| Author | Carey, Mark Shepherd, Trevor G Itamochi, Hiroaki Lee, Wonjae Valdes, Yudith Ramos Hirte, Hal Kolendowski, Bart DiMattia, Gabriel E |
| AuthorAffiliation | 2 Lawson Health Research Institute, London, ON N6C 2R5, Canada 3 Juravinski Cancer Centre, Hamilton, ON L8V 5C2, Canada; hirteh@hhsc.ca 7 Department of Oncology, Western University, London, ON N6A 5W9, Canada 4 Department of Obstetrics and Gynecology, Tottori University School of Medicine, Nishi-cho, Yonago-shi, Tottori-ken 683-0826, Japan; itamochi@hotmail.com 8 Department of Anatomy & Cell Biology, Western University, London, ON N6A 3K7, Canada 5 Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8P 1H6, Canada 6 Department of Obstetrics & Gynaecology, University of British Columbia, Vancouver, BC V6Z 2K8, Canada; mark.carey@ubc.ca 9 Department of Obstetrics & Gynaecology, Western University, London, ON N6H 5W9, Canada 10 Department of Biochemistry, Western University, London, ON N6A 5C1, Canada 1 Mary & John Knight Translational Ovarian Cancer Research Unit, London Regional Cancer Program, London, ON N6A 5W9, Canada; bkolendo@uwo.ca (B.K.); yudithramos@yahoo.es (Y.R.V |
| AuthorAffiliation_xml | – name: 4 Department of Obstetrics and Gynecology, Tottori University School of Medicine, Nishi-cho, Yonago-shi, Tottori-ken 683-0826, Japan; itamochi@hotmail.com – name: 1 Mary & John Knight Translational Ovarian Cancer Research Unit, London Regional Cancer Program, London, ON N6A 5W9, Canada; bkolendo@uwo.ca (B.K.); yudithramos@yahoo.es (Y.R.V.); wlee377@uwo.ca (W.L.); tshephe6@uwo.ca (T.G.S.) – name: 7 Department of Oncology, Western University, London, ON N6A 5W9, Canada – name: 5 Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8P 1H6, Canada – name: 10 Department of Biochemistry, Western University, London, ON N6A 5C1, Canada – name: 6 Department of Obstetrics & Gynaecology, University of British Columbia, Vancouver, BC V6Z 2K8, Canada; mark.carey@ubc.ca – name: 3 Juravinski Cancer Centre, Hamilton, ON L8V 5C2, Canada; hirteh@hhsc.ca – name: 9 Department of Obstetrics & Gynaecology, Western University, London, ON N6H 5W9, Canada – name: 2 Lawson Health Research Institute, London, ON N6C 2R5, Canada – name: 8 Department of Anatomy & Cell Biology, Western University, London, ON N6A 3K7, Canada |
| Author_xml | – sequence: 1 givenname: Bart orcidid: 0000-0003-0607-5858 surname: Kolendowski fullname: Kolendowski, Bart organization: Lawson Health Research Institute, London, ON N6C 2R5, Canada – sequence: 2 givenname: Yudith Ramos surname: Valdes fullname: Valdes, Yudith Ramos organization: Lawson Health Research Institute, London, ON N6C 2R5, Canada – sequence: 3 givenname: Hal surname: Hirte fullname: Hirte, Hal organization: Juravinski Cancer Centre, Hamilton, ON L8V 5C2, Canada – sequence: 4 givenname: Hiroaki orcidid: 0000-0002-7417-8595 surname: Itamochi fullname: Itamochi, Hiroaki organization: Department of Obstetrics and Gynecology, Tottori University School of Medicine, Nishi-cho, Yonago-shi, Tottori-ken 683-0826, Japan – sequence: 5 givenname: Wonjae surname: Lee fullname: Lee, Wonjae organization: Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8P 1H6, Canada – sequence: 6 givenname: Mark surname: Carey fullname: Carey, Mark organization: Department of Obstetrics & Gynaecology, University of British Columbia, Vancouver, BC V6Z 2K8, Canada – sequence: 7 givenname: Trevor G surname: Shepherd fullname: Shepherd, Trevor G organization: Department of Obstetrics & Gynaecology, Western University, London, ON N6H 5W9, Canada – sequence: 8 givenname: Gabriel E surname: DiMattia fullname: DiMattia, Gabriel E organization: Department of Biochemistry, Western University, London, ON N6A 5C1, Canada |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33153119$$D View this record in MEDLINE/PubMed |
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| Keywords | OCCC ovarian clear cell mTOR inhibitor cancer epithelial ovarian cancer cell line spheroid |
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| SubjectTerms | cancer cell line Cell lines clear cell Development and progression Genetic aspects Health aspects mTOR inhibitor Mutation (Biology) ovarian Ovarian cancer spheroid |
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| Title | Characterization of Mutational Status, Spheroid Formation, and Drug Response of a New Genomically-Stable Human Ovarian Clear Cell Carcinoma Cell Line, 105C |
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