Perturbation of adhesive interactions at cell-substratum and cell-cell contact sites is a critical event in the multistep process of cancer invasion. We have previously shown that the urokinase receptor can simultaneously bind to the ammo-terminal fragment (ATI1) of urokinase and to the matrix-like form of vitronectin in cultured cell lines and in breast carcinomas. This interaction occurs at physiological concentrations of the reagents and results in the formation of ternary high Mr complexes (Carrière et al. Clin Cancer Res 1997, in press). To test the involvement of vitronectin receptor to a such complex array of interactions on the cell surface, we simultaneously determined the expression of uPAR, vitronectin and vitronectin receptor αvβ3 and αvβ5 in HT 1080 fibrosarcoma cells, MCF-7 and MDA-MB 231 human breast carcinoma cell lines, bearing high levels of uPAR and all capable of forming high Mr ternary complexes. Immunostaining with a panel of monoclonal antibodies showed a co-ordinate overexpression of uPAR and αvβ5 in the cell lines tested, whereas only a faint reaction could be observed with anti-αvβ3 monoclonal antibody. Then we compared the histological localization of uPAR, vitronectin and vitronectin receptors αvβ3 and αvβ5 in frozen sections of 35 breast carcinomas and 8 benign breast lesions using the same panel of monoclonal antibodies. We found that uPAR-overexpressing breast cancer cells showed a strong chromogenic reaction with anti-αvβ5 monoclonal antibody whereas a positive immunostaining with anti-αvβ3 monoclonal antibody was observed only at the level of endothelial cells.On the contrary, ductal cells in benign breast lesions showed undetectable levels of uPAR and a markedly staining with both αvβ3 and αvβ5 antibodies. Our study showed a co-ordinate overexpression of uPAR and αvβS vitronectin receptor in both cultured cell lines and breast carcinomas supporting the hypothesis of its cooperation to uPAR-dependent regulation of cell adhesion and invasiveness.
|Number of pages||1|
|Journal||Fibrinolysis and Proteolysis|
|Issue number||SUPPL. 3|
|Publication status||Published - 1997|
ASJC Scopus subject areas