Knockout of alpha6 beta1-integrin expression reverses the transformed phenotype of hepatocarcinoma cells
Department of Cancer Biology
Antigens, CD; Carcinoma, Hepatocellular; Cell Adhesion; Cell Division; Cell Movement; Cell Transformation, Neoplastic; *Gene Deletion; Humans; Integrin alpha6beta1; Integrin beta4; Integrins; Liver Neoplasms; Neoplasm Invasiveness; Peptide Fragments; Phenotype; Receptors, Laminin; Transfection; Tumor Cells, Cultured
BACKGROUND and AIMS: Hepatocellular carcinoma is a common complication in liver cirrhosis. The integrin alpha6 beta1, a receptor for the laminin family of extracellular matrix proteins, has been found to be overexpressed in hepatocarcinoma. In an effort to further characterize the involvement of alpha6 beta1-integrin in hepatocarcinoma progression and to study alpha6 beta1-mediated functions, a human hepatocarcinoma cell line, HepG2, that express high surface levels of alpha6 beta1 and uses only this integrin to mediate adhesion on laminin was identified.
METHODS: To assess the role of alpha6 beta1 in these cells, a cytoplasmic domain deletion mutant of the beta4-integrin subunit by complementary DNA transfection was expressed. The expression of the mutant beta4 subunit in association with endogenous alpha6 showed a dominant-negative effect on alpha6 beta1 expression.
RESULTS: Stable transfectants of HepG2 that expressed the mutant beta4 subunit showed a reduced ability to adhere and migrate on laminin matrices and to invade Matrigel. Furthermore, transfected cells showed significantly lower growth rates and reduced anchorage-independent growth compared with mock-transfected cells.
CONCLUSIONS: These findings on the expression and function of alpha6 beta1 in hepatocarcinoma cells emphasize the potential contribution of this laminin receptor in the neoplastic transformation of hepatocytes.
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Citation: Gastroenterology. 1998 Aug;115(2):433-42.
Carloni, Vinicio; Romanelli, Roberto G.; Mercurio, Arthur M.; Pinzani, Massimo; Laffi, Giacomo; Cotrozzi, Giorgio; and Gentilini, Paolo, "Knockout of alpha6 beta1-integrin expression reverses the transformed phenotype of hepatocarcinoma cells" (1998). Cancer Biology Publications and Presentations. Paper 148.