Role of CD44 and Variants in Membrane-Cytoskeleton Interactions, Adhesion, Metastasis and Human Breast Cancers.
Annual rept. 1 Aug 95-31 Jul 96,
MIAMI UNIV FL
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CD44 is the major hyaluronan cell surface receptor, and functions as an adhesion molecule in many different cell types including human breast epithelial cells. The coexpression of certain CD44 variants CD44v, such as CD44v v10ex14, with CD44s standard form appears to be closely associated with human breast tumor metastasis. In this study we have established a stable transfection of CD44v v10ex14 cDNA into normal human breast epithelial cells HBL100 which contain endogenous CD44s. Our results indicate that coexpression of both CD44v v10ex14 and CD44s alters the following important biological properties of these cells a there is a significant reduction in hyaluronic acid HA -mediated cell adhesion b there is an increased migration capability in collagen-matrix gel and c these cells constitutively produce certain angiogenic factors which effectively promote tumorigenesis in athymic nude mice. These findings suggest that coexpression of CD44v v10ex14 and CD44s may trigger the onset of cell transformation required for breast cancer development.
- Medicine and Medical Research