A novel mechanism of colon carcinoma cell adhesion to the endothelium triggered by β1 integrin chain

Inés Martìn-Padura, Gianfranco Bazzoni, Adriana Zanetti, Sergio Bernasconi, Mariano J. Elices, Alberto Mantovani, Elisabetta Dejana

Research output: Contribution to journalArticlepeer-review

Abstract

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 β1-subunit of integrin receptors and antibody blocking experiments showed that α2β1 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 β1 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 β1 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.

Original languageEnglish
Pages (from-to)6124-6132
Number of pages9
JournalJournal of Biological Chemistry
Volume269
Issue number8
Publication statusPublished - Feb 25 1994

ASJC Scopus subject areas

  • Biochemistry

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