Integrin α6β1 plays a significant role in the attachment of hepatoma cells to laminin

Background/Aims: Tumor invasion and metastasis consist of a series of complex events. During this process, the ability of tumor cells to adhere to laminin, a major component of basement membranes, is required at various steps. The expression of laminin-binding integrins and the extent of tumor metastasis and progression appear to be related. In hepatocellular carcinoma, increased expression of laminin-binding integrins is observed. However, little 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 laminin. Methods: Human hepatoma cell lines (KIM-1, KYN-1, 2) were used. We investigated the expression of integrin alpha(1), alpha(2), alpha(3), alpha(6), beta(1) and beta(4) subunits on hepatoma cells by immunocytochemical and flow cytometric analysis. Participation of these integrin subunits in the attachment of hepatoma cells to laminin was evaluated by an inhibition of cell adhesion assay. Results: Integrin alpha(1), alpha(2), alpha(3), alpha(6) and beta(1) subunits were expressed at the marginal areas of hepatoma cells, while the integrin beta(4) subunit was scarcely detected. Laminin promoted the attachment of 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 attachment 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 participation of this integrin in metastasis and invasion of hepatoma cells.