BACKGROUND Integrin-mediated platelet-tumor cell contacting plays an important role in promoting epithelial-mesenchymal transition (EMT) transformation of tumor cells and cancer metastasis, but whether it occurs in breast cancer cells is not completely clear. OBJECTIVE The purpose of this study was to investigate the role of integrin α2β1 in platelet contacting to human breast cancer cell line MCF-7 and its effect on the EMT and the invasion of MCF-7 cells. METHODS Human platelets were activated by thrombin, and separated into pellets and releasates before the co-incubation with MCF-7 cells. Cell invasion was evaluated by transwell assay. The surface integrins on pellets and MCF-7 cells were inhibited by antibodies. The effect of integrin α2β1 on Wnt-β-catenin pathway was assessed by integrin α2β1-silencing and Wnt-β-catenin inhibitor XAV. The therapeutic effect of integrin α2β1-silencing was confirmed in the xenograft mouse model. RESULTS Pellets promote the invasion and EMT of MCF-7 cells via direct contacting of surface integrin α2β1. The integrin α2β1 contacting activates Wnt-β-catenin pathway and promotes the expression of EMT proteins in MCF-7 cells. The activated Wnt-β-catenin pathway also promotes the autocrine of TGF-β1 in MCF-7 cells. Both Wnt-β-catenin and TGF-β1/pSmad3 pathways promote the expression of EMT proteins. Integrin α2β1-silencing inhibits breast cancer metastasis in vivo. CONCLUSIONS The direct interaction between platelets and tumor cells exerts its pro-metastatic function via surface integrin α2β1 contacting and Wnt-β-catenin activation. Integrin α2β1-silencing has the potential effect of inhibiting breast cancer metastasis.

中文翻译：

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血小板通过直接相互作用促进乳腺癌细胞MCF-7转移：表面整合素α2β1接触介导的Wnt-β-catenin途径的激活。

背景技术整联蛋白介导的血小板-肿瘤细胞接触在促进肿瘤细胞的上皮-间质转化（EMT）转化和癌转移中起重要作用，但是它是否在乳腺癌细胞中发生尚不完全清楚。目的研究整联蛋白α2β1在血小板接触人乳腺癌细胞MCF-7中的作用及其对EMT和MCF-7细胞侵袭的影响。方法在与MCF-7细胞共孵育之前，凝血酶激活人血小板，将其分离为沉淀物和释放物。通过transwell测定法评估细胞侵袭。抗体抑制沉淀和MCF-7细胞上的表面整合素。整合素α2β1沉默和Wnt-β-catenin抑制剂XAV评估了整合素α2β1对Wnt-β-catenin途径的影响。在异种移植小鼠模型中证实了整联蛋白α2β1-沉默的治疗作用。结果药丸通过直接接触表面整合素α2β1促进MCF-7细胞的侵袭和EMT。整合素α2β1的接触激活了Wnt-β-catenin途径，并促进了MCF-7细胞中EMT蛋白的表达。激活的Wnt-β-catenin途径还促进MCF-7细胞中TGF-β1的自分泌。Wnt-β-catenin和TGF-β1/ pSmad3途径均可促进EMT蛋白的表达。整联蛋白α2β1沉默可抑制体内乳腺癌的转移。结论血小板与肿瘤细胞之间的直接相互作用通过表面整联蛋白α2β1接触和Wnt-β-catenin活化发挥其促转移功能。整联蛋白α2β1-沉默具有抑制乳腺癌转移的潜在作用。