Integrin alpha(6)beta(1) plays a significant role in the attachment of hepatoma cells to laminin

Background/Aims: Tumor invasion and metastasis consist of a series of compl ex events. During this process, the ability of tumor cells to adhere to lam inin, a major component of basement membranes, is required at various steps . The expression of laminin-binding integrins and the extent of tumor metas tasis and progression appear to be related. In hepatocellular carcinoma, in creased expression of laminin-binding integrins is observed. However, littl e is known concerning the possible functional interactions between laminin- binding integrins and laminin. Therefore, we investigated the participation of laminin-binding integrins in the attachment of hepatoma cells to lamini n. Methods: Human hepatoma cell lines (KIM-1, KYN-1, 2) were used. We investig ated the expression of integrin alpha(1), alpha(2), alpha(3), alpha(6), bet a(1) and beta(4) subunits on hepatoma cells by immunocytochemical and flow cytometric analysis. Participation of these integrin subunits in the attach ment of hepatoma cells to laminin was evaluated by an inhibition of cell ad hesion assay. Results: Integrin alpha(1), alpha(2), alpha(3), alpha(6) and beta(1) subuni ts were expressed at the marginal areas of hepatoma cells, while the integr in beta(4) subunit was scarcely detected. Laminin promoted the attachment o f hepatoma cells in a dose-dependent manner. Although anti-integrin alpha(1 ), alpha(2), alpha(3) and beta(4) subunit antibodies did not inhibit cell a ttachment to laminin, anti-integrin alpha(6) and beta(1) subunit antibodies inhibited the attachment by 50% or more. Conclusions: These findings indicate that integrin alpha(6)beta(1) is very important in the attachment of hepatoma cells to laminin, suggesting the pa rticipation of this integrin in metastasis and invasion of hepatoma cells.