Transforming growth factor-β1 enhances proliferative and metastatic potential by up-regulating lymphoid enhancer-binding factor 1/integrin αMβ2 in human renal cell carcinoma.

Abstract

Renal cell carcinoma (RCC) is a kind of malignant tumor with high recurrence, and it is urgent to find molecular markers for diagnosis and prognosis of RCC. Our study investigated the expression and function of integrin αMβ2 in RCC cells, aiming to understand the role of integrin αMβ2 in RCC and develop new therapeutic target for RCC. Overexpression and knockdown of lymphoid enhancer-binding factor 1 (LEF1) were performed using vector containing full-length cDNA and via siRNA technology, respectively. The expressions of mRNA and protein were detected by RT-PCR and Western blot, respectively. Proliferation of RCC cell was analyzed using WST-1 assay, and metastasis of RCC cell was evaluated using the transwell system. Our results demonstrated that LEF1 and integrin αMβ2 were up-regulated in RCC cells via TGF-β1-dependent mechanism, and LEF1 together with β-catenin directly increased integrin αMβ2 level. On the other hand, TGF-β1-induced proliferation, migration and invasion were suppressed by function-blocking antibody against integrin αMβ2 in RCC cells. In addition, integrin αMβ2 is crucial for LEF1 mediated cell invasion by regulating MMP-2, MMP-9 and calpain-2 secretion in RCC cells. LEF1/integrin αMβ2 expression was regulated by TGF-β1, and LEF1/integrin αMβ2 was involved in TGF-β1's improvement effects on the proliferation and metastasis of RCC. Blocking integrin αMβ2 activity could be a therapeutic option for patients with advanced RCC.