Changes in adhesive and migratory characteristics of hepatocellular carcinoma (HCC) cells induced by expression of α3β1 integrin

The invasive and metastatic potentials of hepatocellular carcinoma are positively correlated with the expression level of α3β1 integrin, a high-affinity adhesion receptor for laminin isoforms including laminin-5. In this study, we investigated changes in the adhesive and invasive behaviors of human HCC HepG2 cells after transfection with cDNA for α3 integrin in order to elucidate the direct involvement of this integrin in these cellular processes. We introduced cDNA for splice variants of α3 integrin (α3A and α3B) into the cells, and selected two transfectant clones (HepG2-3A and HepG2-3B), which express the α3A and α3B integrins, respectively. Both transfectant cells adhered almost equally to laminin-5-coated plates in an α3 integrin-dependent manner, indicating that transfected α3Aβ1 and α3Bβ1 integrins were functionally active in these cells. The migratory and invasive potentials of the transfectant cells were assessed by scratch wound assay and in vitro chemoinvasion assay. The results demonstrated that the migration of HepG2-3A and HepG2-3B cells but not of mock transfectant (HepG2-M) cells was stimulated on the plates coated with laminin-5. Furthermore, HepG2-3A and HepG2-3B cells were found to be more invasive into laminin-5-containing matrices than were HepG2-M cells. These results strongly suggest that enhanced expression of α3β1 integrin on HCC cells is directly involved in their malignant phenotypes such as invasion and metastasis.