| 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). | |
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MedLine Citation:
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PMID: 20470755 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-12 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 397 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-07-08 Completed Date: 2010-08-04 Revised Date: 2013-05-08 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 27-33 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Catalan Institute of Oncology (ICO), Avenida de Francia S/N, Girona, Catalonia, Spain. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies, Monoclonal
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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:
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0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Antigens, CD24; 0/Antigens, CD44; 0/Antineoplastic Agents; P188ANX8CK/trastuzumab |
| Comments/Corrections | |
Comment In:
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Pharmacogenomics. 2011 Jan;12(1):12-3
[PMID:
21213459
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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