A novel mechanism of colon carcinoma cell adhesion to the endothelium triggered by beta 1 integrin chain

• Published in: The Journal of biological chemistry Vol. 269; no. 8; pp. 6124 - 6132
• Main Authors: Martìn-Padura, I, Bazzoni, G, Zanetti, A, Bernasconi, S, Elices, M J, Mantovani, A, Dejana, E
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 25.02.1994
• Subjects: Amino Acid Sequence; Antibodies, Monoclonal - immunology; Cell Adhesion; Cells, Cultured; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Extracellular Matrix Proteins - metabolism; Humans; Integrin beta1; Integrins - immunology; Integrins - metabolism; Molecular Sequence Data; Receptors, Cell Surface - metabolism; Tumor Cells, Cultured
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)37578-6

We have found a monoclonal antibody, called BV7, that rapidly stimulated by 6-10-folds HT-29 colon carcinoma cell adhesion to resting human umbilical vein endothelial cells. This effect was directed to tumor cells and not to endothelial cells and was cell-specific. BV7 was also active on the HCCP-2998 but did not change adhesion to endothelial cells of other tumor cells (MG63 osteosarcoma, A375 melanoma, MHCC-1410 and Lovo colon carcinoma) even if, by flow cytometry, this monoclonal antibody could bind to them. Additionally, BV7 effect was substratum-specific, 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 integrins 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 metabolically active cells. The presence of physiological concentrations of divalent cations and of cytoskeletal integrity was not needed. Comparative studies with eight different prototypic beta 1 antibodies showed 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 the five antibodies recognized a topographically related epitope. Taken together these results provide evidence that beta 1 antibodies may trigger a novel pathway of HT-29 colon carcinoma adhesion to endothelial cells with different features in respect to other described mechanisms of tumor cell interaction with the endothelium.