NOVEL MECHANISM OF COLON-CARCINOMA CELL - ADHESION TO THE ENDOTHELIUMTRIGGERED BY BETA(1) INTEGRIN CHAIN

We have found a monoclonal antibody, called BV7, that rapidly stimulat ed by 6-10-folds HT-29 colon carcinoma cell adhesion to resting human umbilical vein endothelial cells. This effect was directed to tumor ce lls and not to endothelial cells and was cell-specific. BV7 was also a ctive on the HCCP-2998 but did not change adhesion to endothelial cell s of other tumor cells (MG63 osteosarcoma, A375 melanoma, MHCC-1410 an d Love colon carcinoma) even if, by flow cytometry, this monoclonal an tibody could bind to them. Additionally, BV7 effect was substratum-spe cific, since it did not increase but rather blocked HT-29 adhesion to matrix proteins. Immunoprecipitation analysis and binding to specific transfectants revealed that BV7 recognizes beta(1)-subunit of integrin receptors and antibody blocking experiments showed that alpha(2) beta (1) antibodies were able to counteract BV7 effect on HT-29 adhesion to endothelial cells. In contrast, antibodies directed to other integrin s or endothelial adhesive receptors (E- and P-selectin, VCAM-1, ICAM-1 , ICAM-2) were ineffective. Induction of HT-29 adhesion to endothelial cells by BV7 was Fc- and protein synthesis-independent but required m etabolically active cells. The presence of physiological concentration s of divalent cations and of cytoskeletal integrity was not needed, Co mparative studies with eight different prototypic beta(1) antibodies s howed that five of them induced HT-29 adhesion to endothelial cells in a way unrelated to their ability to interfere with HT-29 adhesion to matrix proteins. Cross-blocking binding assays demonstrated that all t he five antibodies recognized a topographically related epitope. Taken together these results provide evidence that beta(1) antibodies may t rigger a novel pathway of HT-29 colon carcinoma adhesion to endothelia l cells with different features in respect to other described mechanis ms of tumor cell interaction with the endothelium.