Document Detail


Dynamic emergence of the mesenchymal CD44(pos)CD24(neg/low) phenotype in HER2-gene amplified breast cancer cells with de novo resistance to trastuzumab (Herceptin).
MedLine Citation:
PMID:  20470755     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Evidence is mounting that the occurrence of the CD44(pos)/CD24(neg/low) cell population, which contains potential breast cancer (BC) stem cells, could explain BC clinical resistance to HER2-targeted therapies. We investigated whether de novo refractoriness to the anti-HER2 monoclonal antibody trastuzumab (Tzb; Herceptin) may relate to the dynamic regulation of the mesenchymal CD44(pos)/CD24(neg/low) phenotype in HER2-positive BC. We observed that the subpopulation of Tzb-refractory JIMT-1 BC cells exhibiting CD44(pos)/CD24(neg/low)-surface markers switched with time. Low-passage JIMT-1 cell cultures were found to spontaneously contain approximately 10% of cells bearing the CD44(pos)/CD24(neg/low) immunophenotype. Late-passage (>60) JIMT-1 cultures accumulated approximately 80% of CD44(pos)/CD24(neg/low) cells and closely resembled the CD44(pos)/CD24(neg/low)-enriched ( approximately 85%) cell population constitutively occurring in HER2-negative MDA-MB-231 mesenchymal BC cells. Dynamic expression of mesenchymal markers was not limited to CD44/CD24 because high-passages of JIMT-1 cells exhibited also reduced expression of the HER2 protein and over-secretion of pro-invasive/metastatic chemokines and metalloproteases. Accordingly, late-passage JIMT-1 cells displayed an exacerbated migratogenic phenotype in plastic, collagen, and fibronectin substrates. Intrinsic genetic plasticity to efficiently drive the emergence of the CD44(pos)/CD24(neg/low) mesenchymal phenotype may account for de novo resistance to HER2 targeting therapies in basal-like BC carrying HER2 gene amplification.
Authors:
Cristina Oliveras-Ferraros; Alejandro Vazquez-Martin; Begoña Martin-Castillo; Silvia Cufí; Sonia Del Barco; Eugeni Lopez-Bonet; Joan Brunet; Javier A Menendez
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-12
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  397     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-07-08     Completed Date:  2010-08-04     Revised Date:  2013-05-08    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  27-33     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Inc. All rights reserved.
Affiliation:
Catalan Institute of Oncology (ICO), Avenida de Francia S/N, Girona, Catalonia, Spain.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / therapeutic use*
Antibodies, Monoclonal, Humanized
Antigens, CD24 / metabolism
Antigens, CD44 / metabolism
Antineoplastic Agents / therapeutic use*
Breast Neoplasms / drug therapy*,  genetics*,  pathology
Cell Line, Tumor
Cell Movement
Drug Resistance, Neoplasm
Female
Gene Amplification*
Gene Expression Regulation, Neoplastic*
Genes, erbB-2*
Humans
Mesoderm / metabolism,  pathology
Neoplastic Stem Cells / drug effects,  metabolism,  physiology
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Antigens, CD24; 0/Antigens, CD44; 0/Antineoplastic Agents; P188ANX8CK/trastuzumab
Comments/Corrections
Comment In:
Pharmacogenomics. 2011 Jan;12(1):12-3   [PMID:  21213459 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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