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DOI: 10.1055/s-0037-1612833
The role of α2, αv and β1 Integrins in cell growth of hepatocellular carcinoma cells in vitro
Publikationsverlauf
Publikationsdatum:
03. Januar 2018 (online)
Background:
The pathogenesis and progression of hepatocellular carcinoma (HCC) are highly associated with A) the proliferative capacity and B) the adhesive and invasive properties of the tumor cells. Invasion of HCC cells requires interactions with the endothelial cells and different components of the extracellular matrix, with integrin adhesion receptors being pivotal elements concerning this process. Integrins represent transmembrane heterodimeric proteins and are composed of different α and β subunits. We hypothesize that integrins not only act on tumor cell invasion but also participate in cell cycle control. Aim of this study was to explore the influence of particular integrin subunits on proliferation activities of HCC cells in vitro.
Methods:
Three Human HCC cell lines, HepG2, Huh7 and Hep3B, were treated with the soluble collagen G and matrigel to activate integrin signaling and cell growth evaluated thereafter by the tetrazolium dye (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT) assay. Cell surface expression of integrin α and β subtypes and cell cycle analysis (BrdU Assay) was assessed by flow cytometry. Cell growth experiments were repeated in the presence of specific integrin inhibitors. Clonogenic growth assay was also employed to evaluate the effect of integrin inhibition on the clonogenic survival of HCC cells.
Results:
Soluble collagen G or matrigel induced a significant increase of HCC cell growth, accompanied by an elevation of the integrin subtypes α2, αv and β1, compared to the untreated controls. Function associated inhibitors of α2, αv and β1 significantly suppressed cell growth evidenced by the MTT assay. Cell cycle arrest in S phase was also observed and clonogenic capacity of HCC cells was downregulated following integrin blockade.
Conclusion:
α2, αv and β1 integrins might be involved in cell growth and cell cycle regulation of HCC cell lines. Targeting these receptors might, therefore, be a novel concept to fight cancer.