机构:[1]Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei 050051[2]Second Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011临床科室外二科河北医科大学第四医院[3]Second Department of Surgery The Bethune International Peace Hospital, Shijiazhuang, Hebei 050082[4]Department of Gynecology and Obstetrics, The Yiwu Affiliated Hospital of Zhejiang University, Yiwu, Zhejiang 322000[5]Department of Surgery, Hebei Medical University Affiliated North China Petroleum Bureau General Hospital, Renqiu, Hebei 062552[6]Centre of Breast Cancer, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China河北医科大学第四医院
The aim of the present study was to examine the role of protease-activated receptor-1 (PAR1)-stimulated platelet activation in the epithelial-mesenchymal transition (EMT) and migration of colon cancer cells, and to identify the underlying mechanisms. TFLLR-NH2, a PAR1 agonist, was used to activate platelets and the platelet supernatants were used to treat the SW620 colon cancer cell line. Expression of E-cadherin and vimentin on SW620 cells was detected by immunofluorescence and western blotting, and the level of the transforming growth factor (31 (TGF-beta 1) was measured using ELISA following the activation of platelets by TFLLR-NH2. miR-200b expression was detected using quantitative PCR in SW620 cells. In order to investigate the chemotactic ability of the SW620 cells, the expression of CXC chemokine receptor type 4 (CXCR4) was measured by flow cytometry. Transwell migration assays were performed following exposure of the cells to the supernatant of PAR1-activated platelets. SW620 cells cultured in the supernatant of TFLLR-NH2-activated platelets upregulated E-cadherin expression and downregulated the vimentin expression. In the in vitro platelet culture system, a TFLLR-NH2 dose-dependent increase of secreted TGF-beta 1 was detected in the supernatant. The activation of PAR1 on the platelets led to the inhibition of miR-200b expression in the SW620 cells that were cultured in platelet-conditioned media. The number of SW620 cells that penetrated through the Transwell membrane increased with the dose of TFLLR-NH2 used to treat the platelets. The percentage of CXCR4-positive SW620 cells was significantly higher when they were exposed to the supernatant of platelets cultured for 24 h with PAR1 agonist than when cultured in non-conditioned media (40.89 +/- 6.74 vs. 3.47 +/- 1.40%, P<0.01). Platelet activation with a PAR1 agonist triggered TGF-beta secretion, which induced EMT of SW620 human colon cancer cells via the downregulation of miR-200b expression, and activated platelets had a chemotactic effect on colon cancer cells mediated by the upregulation of CXCR4 on the cell surface.
基金:
Hebei Province Department of Education Major Project Grant [ZD20131052]
第一作者机构:[1]Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei 050051
通讯作者:
通讯机构:[2]Second Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011[*1]Second Department of Surgery, The Fourth Hospital of Hebei Medical University, 169 Tianshan Road, Shijiazhuang, Hebei 050011, P.R. China
推荐引用方式(GB/T 7714):
Jia Yitao,Zhang Suqiao,Miao Lingling,et al.Activation of platelet protease-activated receptor-1 induces epithelial-mesenchymal transition and chemotaxis of colon cancer cell line SW620[J].ONCOLOGY REPORTS.2015,33(6):2681-2688.doi:10.3892/or.2015.3897.
APA:
Jia, Yitao,Zhang, Suqiao,Miao, Lingling,Wang, Jingbao,Jin, Zujian...&Li, Zhongxin.(2015).Activation of platelet protease-activated receptor-1 induces epithelial-mesenchymal transition and chemotaxis of colon cancer cell line SW620.ONCOLOGY REPORTS,33,(6)
MLA:
Jia, Yitao,et al."Activation of platelet protease-activated receptor-1 induces epithelial-mesenchymal transition and chemotaxis of colon cancer cell line SW620".ONCOLOGY REPORTS 33..6(2015):2681-2688