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Activation of platelet protease-activated receptor-1 induces epithelial-mesenchymal transition and chemotaxis of colon cancer cell line SW620

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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 [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
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关键词: epithelial-mesenchymal transition chemotaxis platelet protease activated receptor-1 transforming growth factor beta 1 colorectal cancer

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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.

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出版当年[2015]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
最新[2025]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
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出版当年[2015]版:
Q3 ONCOLOGY
最新[2023]版:
Q2 ONCOLOGY

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第一作者机构: [1]Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei 050051
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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
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