Overexpression of Integrin-β1 in Leiomyoma Promotes Cell Spreading and Proliferation

Uterine leiomyoma, the most common tumors found in the women of the reproductive age, may cause abnormal uterine bleeding and be life threatening. Compared with myometrium, leiomyoma contains excessive extracellular matrix (ECM). However, the pathological roles of ECM in the development of leiomyoma remain largely unknown. Integrins are the major adhesion molecules on cell surface to interact with ECM. The interactions of ECM with integrins regulate cell adhesion and initiate signals for cell growth, differentiation, and migration.The aim of this study was to investigate the expression and functional role of integrin-β1 in leiomyoma pathogenesis.Levels of integrin-β1 protein were determined by Western blotting in paired normal and leiomyomal tissues (n = 15). Knockdown of integrin-β1 and inhibition of ECM-integrin interaction by disintegrin were used to evaluate the impact of integrin-β1 in cell adhesion, spreading, and proliferation.Levels of integrin-β1 were significantly up-regulated in leiomyomal cells compared with their normal counterparts. Knockdown of integrin-β1 did not affect cell adhesion on fibronectin or laminin matrix but significantly inhibits cell spreading ability. Consistent with this notion, the phosphorylation of focal adhesion kinase and the recruitment of paxillin to the focal contact were decreased in integrin-β1 knockdown cells, which attenuates contraction force. The inability of cell spreading leads to inhibition of cyclin D1 expression and impedes cell cycle progression. More importantly, disruption of ECM-integrin interaction by the small protein, disintegrin inhibited cyclin D1 expression and cell proliferation.These data demonstrate that integrin-β1 is a critical ligand to enhance cell-ECM contact force and thus promotes cell proliferation. Disruption of ECM-integrin-β1 signaling may serve as an option to inhibit the progression of leiomyoma.