کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10764839 1050567 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dynamic emergence of the mesenchymal CD44posCD24neg/low phenotype in HER2-gene amplified breast cancer cells with de novo resistance to trastuzumab (Herceptin)
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Dynamic emergence of the mesenchymal CD44posCD24neg/low phenotype in HER2-gene amplified breast cancer cells with de novo resistance to trastuzumab (Herceptin)
چکیده انگلیسی
Evidence is mounting that the occurrence of the CD44pos/CD24neg/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 CD44pos/CD24neg/low phenotype in HER2-positive BC. We observed that the subpopulation of Tzb-refractory JIMT-1 BC cells exhibiting CD44pos/CD24neg/low-surface markers switched with time. Low-passage JIMT-1 cell cultures were found to spontaneously contain ∼10% of cells bearing the CD44pos/CD24neg/low immunophenotype. Late-passage (>60) JIMT-1 cultures accumulated ∼80% of CD44pos/CD24neg/low cells and closely resembled the CD44pos/CD24neg/low-enriched (∼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 CD44pos/CD24neg/low mesenchymal phenotype may account for de novo resistance to HER2 targeting therapies in basal-like BC carrying HER2 gene amplification.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 397, Issue 1, 18 June 2010, Pages 27-33
نویسندگان
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