Coupling to a cancer-selective heparan-sulfate-targeted branched peptide can by-pass breast cancer cell resistance to methotrexate

Cancer-selective tetra-branched peptides, named NT4, can be coupled to different functional units for cancer cell imaging or therapy. NT4 peptides specifically bind to lipoprotein receptor-related proteins (LRP) receptors and to heparan sulfate chains on membrane proteoglycans and can be efficiently...

Full description

Saved in:
Bibliographic Details
Published inOncotarget Vol. 8; no. 44; pp. 76141 - 76152
Main Authors Depau, Lorenzo, Brunetti, Jlenia, Falciani, Chiara, Scali, Silvia, Riolo, Giulia, Mandarini, Elisabetta, Pini, Alessandro, Bracci, Luisa
Format Journal Article
LanguageEnglish
Published United States Impact Journals LLC 29.09.2017
Subjects
Online AccessGet full text

Cover

Loading…
Abstract Cancer-selective tetra-branched peptides, named NT4, can be coupled to different functional units for cancer cell imaging or therapy. NT4 peptides specifically bind to lipoprotein receptor-related proteins (LRP) receptors and to heparan sulfate chains on membrane proteoglycans and can be efficiently internalized by cancer cells expressing these membrane targets. Since binding and internalization of NT4 peptides is mediated by specific NT4 receptors on cancer cell membranes and this may allow drug resistance produced by drug membrane transporters to be by-passed, we tested the ability of drug-armed NT4 to by-pass drug resistance in cancer cell lines. We found that MTX-conjugated NT4 allows drug resistance to be by-passed in MTX-resistant human breast cancer cells lacking expression of folate reduced carrier. NT4 peptides appear to be extremely promising cancer-selective targeting agents that can be exploited as theranostics in personalized oncological applications.
AbstractList Cancer-selective tetra-branched peptides, named NT4, can be coupled to different functional units for cancer cell imaging or therapy. NT4 peptides specifically bind to lipoprotein receptor-related proteins (LRP) receptors and to heparan sulfate chains on membrane proteoglycans and can be efficiently internalized by cancer cells expressing these membrane targets. Since binding and internalization of NT4 peptides is mediated by specific NT4 receptors on cancer cell membranes and this may allow drug resistance produced by drug membrane transporters to be by-passed, we tested the ability of drug-armed NT4 to by-pass drug resistance in cancer cell lines. We found that MTX-conjugated NT4 allows drug resistance to be by-passed in MTX-resistant human breast cancer cells lacking expression of folate reduced carrier. NT4 peptides appear to be extremely promising cancer-selective targeting agents that can be exploited as theranostics in personalized oncological applications.
Cancer-selective tetra-branched peptides, named NT4, can be coupled to different functional units for cancer cell imaging or therapy. NT4 peptides specifically bind to lipoprotein receptor-related proteins (LRP) receptors and to heparan sulfate chains on membrane proteoglycans and can be efficiently internalized by cancer cells expressing these membrane targets. Since binding and internalization of NT4 peptides is mediated by specific NT4 receptors on cancer cell membranes and this may allow drug resistance produced by drug membrane transporters to be by-passed, we tested the ability of drug-armed NT4 to by-pass drug resistance in cancer cell lines. We found that MTX-conjugated NT4 allows drug resistance to be by-passed in MTX-resistant human breast cancer cells lacking expression of folate reduced carrier. NT4 peptides appear to be extremely promising cancer-selective targeting agents that can be exploited as theranostics in personalized oncological applications.
Author Scali, Silvia
Falciani, Chiara
Bracci, Luisa
Mandarini, Elisabetta
Riolo, Giulia
Depau, Lorenzo
Brunetti, Jlenia
Pini, Alessandro
AuthorAffiliation 1 Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
AuthorAffiliation_xml – name: 1 Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
Author_xml – sequence: 1
  givenname: Lorenzo
  surname: Depau
  fullname: Depau, Lorenzo
  organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
– sequence: 2
  givenname: Jlenia
  surname: Brunetti
  fullname: Brunetti, Jlenia
  organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
– sequence: 3
  givenname: Chiara
  surname: Falciani
  fullname: Falciani, Chiara
  organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
– sequence: 4
  givenname: Silvia
  surname: Scali
  fullname: Scali, Silvia
  organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
– sequence: 5
  givenname: Giulia
  surname: Riolo
  fullname: Riolo, Giulia
  organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
– sequence: 6
  givenname: Elisabetta
  surname: Mandarini
  fullname: Mandarini, Elisabetta
  organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
– sequence: 7
  givenname: Alessandro
  surname: Pini
  fullname: Pini, Alessandro
  organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
– sequence: 8
  givenname: Luisa
  surname: Bracci
  fullname: Bracci, Luisa
  organization: Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
BackLink https://www.ncbi.nlm.nih.gov/pubmed/29100299$$D View this record in MEDLINE/PubMed
BookMark eNpVUclOwzAUtBCItR_ABeXIJeAtiy9IqGKTKnGBs-U4z21QagfbQfTKl-PSsvny1pl51hyhXessIHRK8AWpS0YvndUuKj-HeEEELsoddEgEFzktCrb7Jz9AkxBecHoFr2oq9tEBFQRjKsQh-pi6ceg7O8-iy1SmldXg8wA96Ni9QbaAQXll8zD2RkXIN4LQZk3q6kVKBhhi18IamjWrfFAhpCGoELdsmYa-zzyELsR1Y620hLhw0cN74jxBe0b1ASbbeIyeb2-epvf57PHuYXo9yzUTIuZak7bBHJe4VsbUFFdFS0pgFIgGXQmRqoo3pOJEtcBrw5jR2LCaq7oyGNgxutrwDmOzhFaDjV71cvDdUvmVdKqT_ye2W8i5e5NFWdBSsERwviXw7nWEEOWyC-vPKQtuDJKIEgvKMa_SKtmsau9C8GB-ZAiWX_bJX_vkl30Jc_b3vh_Et1nsE-hBnwQ
CitedBy_id crossref_primary_10_3389_fendo_2018_00069
crossref_primary_10_3390_ijms22147727
crossref_primary_10_1021_acs_molpharmaceut_2c00238
crossref_primary_10_1016_j_jconrel_2018_02_020
crossref_primary_10_1007_s00726_020_02860_1
crossref_primary_10_3892_ol_2018_9617
crossref_primary_10_1080_10837450_2019_1703739
crossref_primary_10_3389_fphar_2023_1052301
crossref_primary_10_3390_jpm11020088
crossref_primary_10_3389_fphar_2023_1188477
crossref_primary_10_1016_j_crphar_2021_100054
crossref_primary_10_1021_acs_jmedchem_0c01848
crossref_primary_10_1016_j_jconrel_2020_12_012
crossref_primary_10_3390_pharmaceutics14071378
crossref_primary_10_3389_fonc_2020_00882
crossref_primary_10_1002_pep2_24089
crossref_primary_10_14233_ajchem_2022_23566
crossref_primary_10_3389_fchem_2022_847573
crossref_primary_10_1039_D0MD00051E
Cites_doi 10.1124/dmd.113.055723
10.1371/journal.pone.0033253
10.1016/j.brainres.2007.02.091
10.1016/j.ygyno.2014.08.023
10.1021/jm400329p
10.1016/j.drup.2012.07.002
10.1016/j.tibs.2014.03.001
10.1042/BJ20111867
10.1309/AJCPZ1D8CALHDXCJ
10.1007/s10555-007-9047-1
10.1038/srep16733
10.1128/MCB.00228-12
10.1017/S1462399409000969
10.1016/j.hoc.2012.02.002
10.1016/j.ejpb.2005.06.001
10.1074/jbc.M103181200
10.1111/j.1582-4934.2010.01236.x
10.1007/s12272-013-0276-2
10.1016/j.addr.2004.01.001
10.1517/14712590802620501
10.1158/1535-7163.MCT-07-0164
10.1007/s10555-007-9046-2
10.1016/S1470-2045(16)30030-4
10.1002/cmdc.200900527
10.1038/nrclinonc.2015.213
10.1038/srep17736
10.1038/nrc3599
10.1074/jbc.M308615200
10.7150/ijms.10497
10.1002/cmdc.201000463
10.1186/1756-9966-33-37
10.1038/srep27174
10.2174/156800910793605875
10.1016/j.tibs.2013.11.002
10.1186/1471-2407-8-124
10.1038/sj.onc.1206946
ContentType Journal Article
Copyright Copyright: © 2017 Depau et al. 2017
Copyright_xml – notice: Copyright: © 2017 Depau et al. 2017
DBID NPM
AAYXX
CITATION
7X8
5PM
DOI 10.18632/oncotarget.19056
DatabaseName PubMed
CrossRef
MEDLINE - Academic
PubMed Central (Full Participant titles)
DatabaseTitle PubMed
CrossRef
MEDLINE - Academic
DatabaseTitleList
MEDLINE - Academic
PubMed
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
DeliveryMethod fulltext_linktorsrc
EISSN 1949-2553
EndPage 76152
ExternalDocumentID 10_18632_oncotarget_19056
29100299
Genre Journal Article
GroupedDBID ---
53G
ADBBV
ADRAZ
AENEX
ALMA_UNASSIGNED_HOLDINGS
AOIJS
BAWUL
DIK
FRJ
GX1
HYE
KQ8
M48
M~E
NPM
OK1
PGMZT
RPM
AAYXX
CITATION
7X8
5PM
ID FETCH-LOGICAL-c399t-cc1db040608aff82075d16e32e1cec799d1674b1741ade48f33fc0f384a87f0e3
IEDL.DBID RPM
ISSN 1949-2553
IngestDate Tue Sep 17 21:12:09 EDT 2024
Fri Aug 16 11:00:59 EDT 2024
Fri Aug 23 00:24:28 EDT 2024
Wed Oct 16 00:59:53 EDT 2024
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed false
IsScholarly true
Issue 44
Keywords drug-resistance
methotrexate
peptides
heparan sulfate
Language English
License This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c399t-cc1db040608aff82075d16e32e1cec799d1674b1741ade48f33fc0f384a87f0e3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
OpenAccessLink https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652693/
PMID 29100299
PQID 1960924047
PQPubID 23479
PageCount 12
ParticipantIDs pubmedcentral_primary_oai_pubmedcentral_nih_gov_5652693
proquest_miscellaneous_1960924047
crossref_primary_10_18632_oncotarget_19056
pubmed_primary_29100299
PublicationCentury 2000
PublicationDate 2017-09-29
PublicationDateYYYYMMDD 2017-09-29
PublicationDate_xml – month: 09
  year: 2017
  text: 2017-09-29
  day: 29
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle Oncotarget
PublicationTitleAlternate Oncotarget
PublicationYear 2017
Publisher Impact Journals LLC
Publisher_xml – name: Impact Journals LLC
References Hou (8) 2014; 42
Scatizzi (12) 2010; 10
Bracci (17) 2016; 6
Emonard (20) 2012; 32
Lehr (33) 2006; 62
Hassan (36) 2016; 17
Harashima (3) 2014; 37
van Kuppevelt (24) 2014; 135
Bracci (35) 2009; 9
Bracci (11) 2010; 5
Bracci (15) 2015; 5
Ratnam (27) 2004; 56
Morelli (13) 2011; 6
Bracci (10) 2007; 6
Deng (26) 2007; 26
Chen (30) 2015; 5
Gorlick (38) 2008; 8
Hou (7) 2008; 79
Guldberg (39) 2001; 276
Machado-Santelli (2) 2014; 33
Bracci (16) 2013; 56
Wu (22) 2013; 44
Wei (23) 2013; 140
Goldman (29) 2007; 26
Groninger (34) 2016; 13
Blobe (19) 2014; 39
Neri (37) 2003; 278
Dolmer (21) 2012; 443
Goldman (5) 2012; 26
Goldman (28) 2009; 11
Lee (25) 2015; 12
Plant (32) 2012; 7
Kerr (4) 2014; 39
Assaraf (6) 2012; 15
Goldman (9) 2003; 22
Roux (31) 2007; 1150
Johnston (1) 2013; 13
Sanderson (18) 2011; 15
Bracci (14) 2015; 2015
References_xml – volume: 42
  start-page: 632
  year: 2014
  ident: 8
  article-title: The major facilitative folate transporters solute carrier 19A1 and solute carrier 46A1: biology and role in antifolate chemotherapy of cancer
  publication-title: Drug Metab Dispos
  doi: 10.1124/dmd.113.055723
  contributor:
    fullname: Hou
– volume: 7
  start-page: e33253
  year: 2012
  ident: 32
  article-title: Characterization of rhodamine-123 as a tracer dye for use in in vitro drug transport assays
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0033253
  contributor:
    fullname: Plant
– volume: 1150
  start-page: 1
  year: 2007
  ident: 31
  article-title: A functional in vitro model of rat blood-brain barrier for molecular analysis of efflux transporters
  publication-title: Brain Res
  doi: 10.1016/j.brainres.2007.02.091
  contributor:
    fullname: Roux
– volume: 135
  start-page: 371
  year: 2014
  ident: 24
  article-title: Sulfated sugars in the extracellular matrix orchestrate ovarian cancer development: ‘When sweet turns sour’
  publication-title: Gynecol Oncol
  doi: 10.1016/j.ygyno.2014.08.023
  contributor:
    fullname: van Kuppevelt
– volume: 56
  start-page: 5009
  year: 2013
  ident: 16
  article-title: Cancer selectivity of tetrabranched neurotensin peptides is generated by simultaneous binding to sulfated glycosaminoglycans and protein receptors
  publication-title: J Med Chem
  doi: 10.1021/jm400329p
  contributor:
    fullname: Bracci
– volume: 15
  start-page: 183
  year: 2012
  ident: 6
  article-title: Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance
  publication-title: Drug Resist Updat
  doi: 10.1016/j.drup.2012.07.002
  contributor:
    fullname: Assaraf
– volume: 39
  start-page: 277
  year: 2014
  ident: 19
  article-title: Heparan sulfate signaling in cancer
  publication-title: Trends Biochem Sci
  doi: 10.1016/j.tibs.2014.03.001
  contributor:
    fullname: Blobe
– volume: 443
  start-page: 65
  year: 2012
  ident: 21
  article-title: A proximal pair of positive charges provides the dominant ligand-binding contribution to complement-like domains from the LRP (low-density lipoprotein receptor-related protein)
  publication-title: Biochem J
  doi: 10.1042/BJ20111867
  contributor:
    fullname: Dolmer
– volume: 140
  start-page: 468
  year: 2013
  ident: 23
  article-title: Syndecan-1 overexpression is associated with nonluminal subtypes and poor prognosis in advanced breast cancer
  publication-title: Am J Clin Pathol
  doi: 10.1309/AJCPZ1D8CALHDXCJ
  contributor:
    fullname: Wei
– volume: 26
  start-page: 129
  year: 2007
  ident: 29
  article-title: The molecular identity and characterization of a Proton-coupled Folate Transporter—PCFT; biological ramifications and impact on the activity of pemetrexed
  publication-title: Cancer Metastasis Rev
  doi: 10.1007/s10555-007-9047-1
  contributor:
    fullname: Goldman
– volume: 5
  start-page: 16733
  year: 2015
  ident: 30
  article-title: Targeted Proteomics Enables Simultaneous Quantification of Folate Receptor Isoforms and Potential Isoform-based Diagnosis in Breast Cancer
  publication-title: Sci Rep
  doi: 10.1038/srep16733
  contributor:
    fullname: Chen
– volume: 32
  start-page: 3293
  year: 2012
  ident: 20
  article-title: LRP-1CD44, a new cell surface complex regulating tumor cell adhesion
  publication-title: Mol Cell Biol
  doi: 10.1128/MCB.00228-12
  contributor:
    fullname: Emonard
– volume: 11
  start-page: e4
  year: 2009
  ident: 28
  article-title: Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues
  publication-title: Expert Rev Mol Med
  doi: 10.1017/S1462399409000969
  contributor:
    fullname: Goldman
– volume: 26
  start-page: 629
  year: 2012
  ident: 5
  article-title: The antifolates
  publication-title: Hematol Oncol Clin North Am
  doi: 10.1016/j.hoc.2012.02.002
  contributor:
    fullname: Goldman
– volume: 62
  start-page: 39
  year: 2006
  ident: 33
  article-title: Development of a fluorescence-based assay for screening of modulators of human organic anion transporter 1B3 (OATP1B3)
  publication-title: Eur J Pharm Biopharm
  doi: 10.1016/j.ejpb.2005.06.001
  contributor:
    fullname: Lehr
– volume: 2015
  start-page: 173507
  year: 2015
  ident: 14
  article-title: Neurotensin branched Peptide as a tumor-targeting agent for human bladder cancer
  publication-title: Biomed Res Int
  contributor:
    fullname: Bracci
– volume: 276
  start-page: 39990
  year: 2001
  ident: 39
  article-title: Methylation-dependent silencing of the reduced folate carrier gene in inherently methotrexate-resistant human breast cancer cells
  publication-title: J Biol Chem
  doi: 10.1074/jbc.M103181200
  contributor:
    fullname: Guldberg
– volume: 15
  start-page: 1013
  year: 2011
  ident: 18
  article-title: Proteoglycans in cancer biology, tumour microenvironment and angiogenesis
  publication-title: J Cell Mol Med
  doi: 10.1111/j.1582-4934.2010.01236.x
  contributor:
    fullname: Sanderson
– volume: 37
  start-page: 4
  year: 2014
  ident: 3
  article-title: Cancer multidrug resistance: mechanisms involved and strategies for circumvention using a drug delivery system
  publication-title: Arch Pharm Res
  doi: 10.1007/s12272-013-0276-2
  contributor:
    fullname: Harashima
– volume: 56
  start-page: 1067
  year: 2004
  ident: 27
  article-title: Distribution, functionality and gene regulation of folate receptor isoforms: implications in targeted therapy
  publication-title: Adv Drug Deliv Rev
  doi: 10.1016/j.addr.2004.01.001
  contributor:
    fullname: Ratnam
– volume: 9
  start-page: 171
  year: 2009
  ident: 35
  article-title: Oligo-branched peptides for tumor targeting: from magic bullets to magic forks
  publication-title: Expert Opin Biol Ther
  doi: 10.1517/14712590802620501
  contributor:
    fullname: Bracci
– volume: 6
  start-page: 2441
  year: 2007
  ident: 10
  article-title: Synthesis and biological activity of stable branched neurotensin peptides for tumor targeting
  publication-title: Mol Cancer There
  doi: 10.1158/1535-7163.MCT-07-0164
  contributor:
    fullname: Bracci
– volume: 26
  start-page: 111
  year: 2007
  ident: 26
  article-title: Human reduced folate carrier: translation of basic biology to cancer etiology and therapy
  publication-title: Cancer Metastasis Rev
  doi: 10.1007/s10555-007-9046-2
  contributor:
    fullname: Deng
– volume: 17
  start-page: e254
  year: 2016
  ident: 36
  article-title: Antibody-drug conjugates for cancer therapy
  publication-title: Lancet Oncol
  doi: 10.1016/S1470-2045(16)30030-4
  contributor:
    fullname: Hassan
– volume: 5
  start-page: 567
  year: 2010
  ident: 11
  article-title: Design andevaluation of branched peptide conjugates: turning nonspecific cytotoxic drugs into tumor-selective agents
  publication-title: Chem Med Chem
  doi: 10.1002/cmdc.200900527
  contributor:
    fullname: Bracci
– volume: 13
  start-page: 209
  year: 2016
  ident: 34
  article-title: Kinase inhibitors and monoclonal antibodies in oncology: clinical implications
  publication-title: Nat Rev Clin Oncol
  doi: 10.1038/nrclinonc.2015.213
  contributor:
    fullname: Groninger
– volume: 5
  start-page: 17736
  year: 2015
  ident: 15
  article-title: Tumor-selective peptide-carrier delivery of Paclitaxel increases in vivo activity of the drug
  publication-title: Sci Rep
  doi: 10.1038/srep17736
  contributor:
    fullname: Bracci
– volume: 13
  start-page: 714
  year: 2013
  ident: 1
  article-title: Cancer drug resistance: an evolving paradigm
  publication-title: Nat Rev Cancer
  doi: 10.1038/nrc3599
  contributor:
    fullname: Johnston
– volume: 79
  start-page: 145
  year: 2008
  ident: 7
  article-title: Structure and function of the reduced folate carrier a paradigm of a major facilitator superfamily mammalian nutrient transporter
  publication-title: Vitam Horm
  contributor:
    fullname: Hou
– volume: 278
  start-page: 46590
  year: 2003
  ident: 37
  article-title: Synthetic peptides in the form of dendrimers become resistant to protease activity
  publication-title: J Biol Chem
  doi: 10.1074/jbc.M308615200
  contributor:
    fullname: Neri
– volume: 12
  start-page: 92
  year: 2015
  ident: 25
  article-title: Syndecan-1 expression is associated with tumor size and EGFR expression in colorectal carcinoma: a clinicopathological study of 230 cases
  publication-title: Int J Med Sci
  doi: 10.7150/ijms.10497
  contributor:
    fullname: Lee
– volume: 6
  start-page: 678
  year: 2011
  ident: 13
  article-title: Target-selective drug delivery through liposomes labeled with oligobranched neurotensin peptides
  publication-title: Chem Med Chem
  doi: 10.1002/cmdc.201000463
  contributor:
    fullname: Morelli
– volume: 33
  start-page: 37
  year: 2014
  ident: 2
  article-title: The multiple facets of drug resistance: one history, different approaches
  publication-title: J Exp Clin Cancer Res
  doi: 10.1186/1756-9966-33-37
  contributor:
    fullname: Machado-Santelli
– volume: 6
  start-page: 27174
  year: 2016
  ident: 17
  article-title: Insights into the role of sulfated glycans in cancer cell adhesion and migration through use of branched peptide probe
  publication-title: Sci Rep
  doi: 10.1038/srep27174
  contributor:
    fullname: Bracci
– volume: 10
  start-page: 695
  year: 2010
  ident: 12
  article-title: Modular branched neurotensin peptides for tumor target tracing and receptor-mediated therapy: a proof-of-concept
  publication-title: Curr Cancer Drug Targets
  doi: 10.2174/156800910793605875
  contributor:
    fullname: Scatizzi
– volume: 39
  start-page: 8
  year: 2014
  ident: 4
  article-title: Towards understanding promiscuity in multidrug efflux pumps
  publication-title: Trends Biochem Sci
  doi: 10.1016/j.tibs.2013.11.002
  contributor:
    fullname: Kerr
– volume: 8
  start-page: 124
  year: 2008
  ident: 38
  article-title: Quantitative correlation between promoter methylation and messenger RNA levels of the reduced folate carrier
  publication-title: BMC Cancer
  doi: 10.1186/1471-2407-8-124
  contributor:
    fullname: Gorlick
– volume: 22
  start-page: 7431
  year: 2003
  ident: 9
  article-title: Resistance to antifolates
  publication-title: Oncogene
  doi: 10.1038/sj.onc.1206946
  contributor:
    fullname: Goldman
– volume: 44
  start-page: 542
  year: 2013
  ident: 22
  article-title: Glypican-3: a marker and a therapeutic target in hepatocellular carcinoma
  publication-title: Hum Pathol
  contributor:
    fullname: Wu
SSID ssj0000547829
Score 2.3251176
Snippet Cancer-selective tetra-branched peptides, named NT4, can be coupled to different functional units for cancer cell imaging or therapy. NT4 peptides specifically...
SourceID pubmedcentral
proquest
crossref
pubmed
SourceType Open Access Repository
Aggregation Database
Index Database
StartPage 76141
SubjectTerms Research Paper
SummonAdditionalLinks – databaseName: Scholars Portal Open Access Journals
  dbid: M48
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwdV3BTtwwELUovfRSgSh0W0BG6gnJkNiOEx8QQqgIIdFTV-IWxfaYrYSSZTcrLVe-nJkkS6HQWxTHk8TPzryJ7TeM_Ugt-CRoKXQwidAuKGFNAJEpdN8VfjazSPudr3-Zy7G-uslu1tgqvdXQgPN3QzvKJzWe3R0t7x9OccCf0IAvjJLHDekYdAunj9C_ZeYD-yg1Buq0km9g-73Ut0Z_aIe5zXdrkjawJVXSTgv2haN6wz7_XUT5witdbLDPA53kZz3-m2wN6i32eN4saKPtLW8bXnFPwM7EvMt4gx83PgES_K7FfHEXkWqK_tEgcEdZNiZ4MKW1LgGoKncPYooMGwspzc9gjdMPf46hOtFPPEF36pJRtzNYos0vbHzx8_f5pRhyLQiPFKUV3qfB4YA2SVHFiLQgz0JqQElIPfjc2kDbFRzGL2kVQBdRqeiTqApdFXlMQG2z9bqp4Svjroq5DD7PixB1JqNzOkDmM4jRKC_tiB2uGrac9pIaJYUiBEj5F5CyA2TEDlZNX2LHp5eramgWcyw2CQaPic5HbKeH4tncCsMRy1-B9HwBiWq_Lqn_TDpxbSS40lj17b82v7NPklw7zUzZXbbezhawh8Skdftdd3sCSs3ovA
  priority: 102
  providerName: Scholars Portal
Title Coupling to a cancer-selective heparan-sulfate-targeted branched peptide can by-pass breast cancer cell resistance to methotrexate
URI https://www.ncbi.nlm.nih.gov/pubmed/29100299
https://search.proquest.com/docview/1960924047
https://pubmed.ncbi.nlm.nih.gov/PMC5652693
Volume 8
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1La9wwEBbZnHopDelj2zSo0FNBu7Zeto5laRIKW3poYG_GenUDib3seqG99pd3RraTTXrrxRjLkmXNWPONNfqGkI-5CS7zkjPpdcak9YIZ7QNTAsx3DdOmirjfeflNX13Lryu1OiJq3AuTgvadvZk1t3ez5madYis3d24-xonNvy8XAEK4NmI-IRNQ0AMXvSf0lmD1zLCCWWrB5y3yHKTA6hnYP4Vpi7hB7tHE-Hpgjv7BmE9DJQ9sz8UL8nwAjfRz37kTchSaU_Jn0e5xO-1P2rW0pg7Ft2W7lNcGpjC6Dkjr3bDd_jYCoGR914KnFnNprOFkgxEtPmBVan-zDeBoKMRkPkNrFH_rU3DIEWTCBXxSSjndbcMvaPMlub748mNxxYaMCswBEOmYc7m38NnqrKxjBONfKJ_rIHjIXXCFMR43JVjwUvLaB1lGIaLLoihlXRYxC-IVOW7aJrwh1Nax4N4VRemjVDxaK31QToUYtXDcTMmncWCrTU-cUaHDgQKpHgRSJYFMyYdx6CtQb3y5ugntfgfFOgMXMZPFlLzuRXHf3CjDKSkeCen-BqTOflwCGpUotAcNevvfNd-RZxwNPK5PmTNy3G334T3Ak86ek8nlKofjUpbnSTX_ArxO7rE
link.rule.ids 230,315,730,783,787,888,2228,24330,27936,27937,53804,53806
linkProvider National Library of Medicine
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwELZKOcClFPHo8jQSJyRnEz-S-IhWVAt0Kw4t6i2KX2xFm6x2Ewk48suZyaPdlhPcojh2Yn2O5xt55htC3iba29hJzqRLYyaNE0ynzjMlwHyXsG2qgPnOi-N0fio_namzHaLGXJguaN-a86i6uIyq82UXW7m6tNMxTmz6ZTEDEsJTLaZ3yF34X2O55aT3kt4S7J4ezjDzVPBpjUoHXWh1BBZQYeEirlF9tNN83TJIf7HM28GSW9bn8AH5On53H3TyPWobE9lftyQd_3li-2Rv4KP0fd_8kOz46hH5PatbzNT9RpualtTiylizTVcyB3ZHuvSoGF6xTXsRgKuyfs7eUYNlOpZwscJgGeexKzU_2QooOjRinaBhNIonBhR8feSvcAPf1FWzbtb-B4z5mJwefjiZzdlQrIFZ4DgNszZxBnaENM7LEIBXZMolqRfcJ9bbTGuH-Q4GHKCkdF7mQYhg4yByWeZZiL14QnaruvIHhJoyZNzZLMtdkIoHY6TzyiofQios1xPybkSsWPWaHAX6Moh0cY100SE9IW9GTAv4c3ByZeXrdgPNaQzeZyyzCXnaY3w13Lg4JiS7gf7VA6jKfbMFMO3UuQcMn_13z9fk3vxkcVQcfTz-_Jzc58gj8BhMvyC7zbr1L4EFNeZVt-b_AAhEDu8
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwELagSIgLLeK1lIKROCE5LztOckQLq_Jo1QOVKi5R_OpWtEm0m0gtR345M05StuXWWxQ_EuuzPd_I428IeR8XVkdGJEwYGTGhDGeFNJalHMx3Bdtm6vC-88Gh3D8WX0_Sk41UXz5oX6uzoD6_COqzpY-tbC90OMWJhUcHcyAhiSx42BoX3icPYM1GcsNRH2S9Bdi-YjzHzCVPwgbVDnx4dQBWMMXkRUmBCqRe93XDKP3HNG8HTG5YoMU2-Tn9-xB48ivoOxXo37dkHe80uB3yeOSl9ONQ5Qm5Z-un5M-86fHG7intGlpRjTNkxdY-dQ7sknRpUTm8Zuv-3AFnZcO4raEK03Us4aHFoBljsSlVV6wFqg6FmC9o7I3iyQEFnx95LLzAL_ms1t3KXkKfz8jx4vOP-T4bkzYwDVynY1rHRsHOIKO8cg74RZaaWFqe2FhbnRWFwXsPChyhuDJW5I5zpyPHc1HlmYssf0626qa2LwlVlcsSo7MsN06kiVNKGJvq1DonuU6KGfkwoVa2gzZHiT4Nol3-Q7v0aM_IuwnXElYQDq6qbdOvoVhG4IVGIpuRFwPO191NE2RGshsz4LoCqnPfLAFcvUr3iOOrO7d8Sx4efVqU378cftsljxKkE3gaVrwmW92qt3tAhjr1xk_7v00hEW8
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=Coupling+to+a+cancer-selective+heparan-sulfate-targeted+branched+peptide+can+by-pass+breast+cancer+cell+resistance+to+methotrexate&rft.jtitle=Oncotarget&rft.au=Depau%2C+Lorenzo&rft.au=Brunetti%2C+Jlenia&rft.au=Falciani%2C+Chiara&rft.au=Scali%2C+Silvia&rft.date=2017-09-29&rft.eissn=1949-2553&rft.volume=8&rft.issue=44&rft.spage=76141&rft_id=info:doi/10.18632%2Foncotarget.19056&rft_id=info%3Apmid%2F29100299&rft.externalDocID=29100299
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1949-2553&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1949-2553&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1949-2553&client=summon