title: Changes in adhesive and migratory characteristics of hepatocellular carcinoma (HCC) cells induced by expression of alpha3beta1 integrin.
abstract: 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.
authors.affiliation: Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Mizuno
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ogura
authors.forename: Yuta
authors.initials: Y
authors.lastname: Saito
authors.forename: Wakana
authors.initials: W
authors.lastname: Sekine
authors.forename: Rikio
authors.initials: R
authors.lastname: Sano
authors.forename: Toshie
authors.initials: T
authors.lastname: Gotou
authors.forename: Teruaki
authors.initials: T
authors.lastname: Oku
authors.forename: Saotomo
authors.initials: S
authors.lastname: Itoh
authors.forename: Kouji
authors.initials: K
authors.lastname: Katabami
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tsuji
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D039201:Integrin alpha3beta1 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D014162:Transfection
chemical_list: D016326:Extracellular Matrix Proteins; D039201:Integrin alpha3beta1