EXPRESSION AND LIGAND-BINDING OF ALPHA-2-BETA-1 INTEGRIN ON BREAST-CARCINOMA CELLS

We examined the expression and ligand specificity of the alpha 2 beta 1 integrin on human mammary epithelial cells (HMEC) and a panel of bre ast carcinoma cell lines in vitro. We found that the alpha 2 beta 1 in tegrin was universally, but quite variably expressed on these cells by FACS analysis. No significant correlation was observed between its ex pression and other known cellular phenotypes. Substrate attachment ass ays using blocking antibodies demonstrated that alpha 2 beta 1 integri n served as a receptor for collagen on HMEC and almost all breast carc inoma cells. However, its contribution to laminin binding of these cel ls appeared to be related to cellular differentiation as evaluated by sex steroid receptor status and by markers of epithelial-mesenchymal t ransition, i.e. loss of E-cadherin and expression of vimentin. Two dif ferent populations of non-malignant immortalized HMEC (184A1N4 and MCF -10A) contained cells capable of using alpha 2 beta 1 integrin as a la minin receptor. Breast cancer cell lines positive for estrogen recepto r (ER) and E-cadherin (MCF-7, T47D, ZR75-1) could also use alpha 2 bet a 1 integrin as a laminin receptor. Conversely, alpha 2 beta 1 integri n appeared to be incapable of binding to laminin or to be a very minor receptor for laminin on metastatic ER-negative breast carcinoma cells that expressed vimentin (MDA-MB 231, MDA-MB 435, and MDA-MB 436). The se findings suggest that the ligand specificity of alpha 2 beta 1 inte grin, i.e. its function as a laminin receptor, may be regulated during the malignant progression of breast carcinoma cells. A reduced contri bution of alpha 2 beta 1 integrin to the cellular laminin binding appe ars to be associated with an increased malignant phenotype and with an epithelial-mesenchymal transition of breast carcinoma cells.