The invasive and metastatic potentials of
hepatocellular carcinoma are positively correlated with the expression level of
alpha3beta1 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
alpha3 integrin in order to elucidate the direct involvement of this
integrin in these cellular processes. We introduced
cDNA for splice variants of
alpha3 integrin (alpha3A and alpha3B) into the cells, and selected two transfectant clones (HepG2-3A and HepG2-3B), which express the alpha3A and alpha3B
integrins, respectively. Both transfectant cells adhered almost equally to laminin-5-coated plates in an
alpha3 integrin-dependent manner, indicating that transfected alpha3Abeta1 and alpha3Bbeta1
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
alpha3beta1 integrin on HCC cells is directly involved in their malignant phenotypes such as invasion and
metastasis.