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Platelets Promote Breast Cancer Cell MCF-7 Metastasis by Direct Interaction: Surface Integrin α2β1 Contacting Mediated Activation of Wnt-β-Catenin Pathway
30 Pages Posted: 23 Jun 2019
More...Abstract
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.
Funding: This study was supported by the National Natural Science Foundation of China (Grant No. 81702595).
Declaration of Interest: All authors declare that they have no competing interests.
Ethical Approval: This study was approved by the Institute Research Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University. All the individuals were participating in this study with written informed consent. All animals-treatment operations were executed according to the Zhengzhou University Ethical Guidelines for Animal Experiment.
Keywords: epithelial-mesenchymal transition; platelet; direct interaction; MCF-7 cell; Wnt-β-catenin; TGF-β1; integrin α2β1
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