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.

中文翻译：

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转化生长因子-β1通过上调人肾细胞癌中的淋巴增强剂结合因子1 /整合素αMβ2来增强增殖和转移潜能。

肾细胞癌（RCC）是一种高复发率的恶性肿瘤，迫切需要寻找可用于诊断和预后的分子标志物。我们的研究调查了整合素αMβ2在RCC细胞中的表达和功能，旨在了解整合素αMβ2在RCC中的作用，并为RCC开发新的治疗靶标。分别使用包含全长cDNA的载体和通过siRNA技术进行淋巴增强剂结合因子1（LEF1）的过表达和敲除。RT-PCR和Western blot检测mRNA和蛋白的表达。使用WST-1分析法分析RCC细胞的增殖，并使用transwell系统评估RCC细胞的转移。我们的研究结果表明，LEF1和整联蛋白αMβ2通过TGF-β1依赖性机制在RCC细胞中被上调，和LEF1与β-catenin一起直接增加整联蛋白αMβ2的水平。另一方面，在RCC细胞中，针对整合素αMβ2的功能阻断抗体抑制了TGF-β1诱导的增殖，迁移和侵袭。此外，整联蛋白αMβ2通过调节RCC细胞中的MMP-2，MMP-9和钙蛋白酶-2分泌对于LEF1介导的细胞侵袭至关重要。TGF-β1调节LEF1 /整合素αMβ2的表达，而LEF1 /整合素αMβ2参与TGF-β1对RCC增殖和转移的改善作用。阻断整联蛋白αMβ2的活性可能是晚期RCC患者的治疗选择。整联蛋白αMβ2通过调节RCC细胞中的MMP-2，MMP-9和calpain-2分泌对于LEF1介导的细胞侵袭至关重要。TGF-β1调节LEF1 /整合素αMβ2的表达，而LEF1 /整合素αMβ2参与TGF-β1对RCC增殖和转移的改善作用。阻断整联蛋白αMβ2的活性可能是晚期RCC患者的治疗选择。整联蛋白αMβ2通过调节RCC细胞中的MMP-2，MMP-9和calpain-2分泌对于LEF1介导的细胞侵袭至关重要。TGF-β1调节LEF1 /整合素αMβ2的表达，而LEF1 /整合素αMβ2参与TGF-β1对RCC增殖和转移的改善作用。阻断整联蛋白αMβ2的活性可能是晚期RCC患者的治疗选择。