COLLAGEN-INDUCED RAPID MORPHOGENESIS OF HUMAN MAMMARY EPITHELIAL-CELLS - THE ROLE OF THE ALPHA-2-BETA-1 INTEGRIN

The cell line MTSV1-7, originally derived by immortalizing mammary epithelial cells cultured from human milk was able to form three-dimensional structures in collagen gel. We have now found that these cells, cultured as a monolayer, are able to undergo rapid morphogenesis forming ridges and balls around collagen fibres, when soluble collagen type I is added to the medium. Monoclonal antibodies to the alpha-2(P1E6) and beta-1-(mAB13) subunits of VLA-2, but not to the alpha-3-subunit (P1B5) of VLA-3, could block this collagen-induced rapid morphogenesis (CIRM). The effect of the antibodies on cell attachment, spreading, and migration on collagen gels was analyzed to identify alpha-2-beta-1 dependent steps which might be involved in CIRM. The results suggest that while other proteins, besides alpha-2-beta-1, are also involved in cell attachment and migration, cell spreading was specifically blocked by antibodies to the VLA-2, but not to the VLA-3 integrin. The results demonstrate that the alpha-2-beta-1 integrin plays a crucial role in the collagen-induced morphogenesis of human mammary epithelial cells and implicate the process of VLA-2-dependent cell spreading as an important step in this morphogenesis.