Platelets promote breast cancer cell MCF-7 metastasis by direct interaction: surface integrin ?2?1-contacting-mediated activation of Wnt-?-catenin pathway.

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 ?2?1 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 ?2?1 on Wnt-?-catenin pathway was assessed by integrin ?2?1-silencing and Wnt-?-catenin inhibitor XAV. The therapeutic effect of integrin ?2?1-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 ?2?1. The integrin ?2?1 contacting activates Wnt-?-catenin pathway and promotes the expression of EMT proteins in MCF-7 cells. The activated Wnt-?-catenin pathway also promotes the autocrine of TGF-?1 in MCF-7 cells. Both Wnt-?-catenin and TGF-?1/pSmad3 pathways promote the expression of EMT proteins. Integrin ?2?1-silencing inhibits breast cancer metastasis in vivo. CONCLUSIONS:The direct interaction between platelets and tumor cells exerts its pro-metastatic function via surface integrin ?2?1 contacting and Wnt-?-catenin activation. Integrin ?2?1-silencing has the potential effect of inhibiting breast cancer metastasis.

SUBMITTER: Zuo XX 

PROVIDER: S-EPMC6836423 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature