摘要
目的:探讨血小板和血小板P-选择素(P-selectin)与肺癌临床病理特征、血行转移及预后的关系,并研究活化血小板表面P-selectin与其配体P-选择素糖蛋白配体1(PSGL-1)对肺癌血行转移相关整合素β3(ITGB3)的影响及作用机制。方法:流式细胞术检测活化血小板表面P-selectin水平,并分析其与肺癌的关系和血行转移风险;Western blot检测不同类型肺癌组织和细胞中PSGL-1的表达情况;通过体外共培养血小板和肺癌细胞,观察PSGL-1上调或抑制对肺癌细胞侵袭和迁移的影响;研究不同干预因素的血小板和肺癌细胞共培养后,肺癌细胞ITGB3的表达变化情况。结果:与对照组比较,肺癌患者血小板计数和血小板表面P-selectin的水平升高(P<0.05),且血小板P-selectin的水平与肺癌血行转移存在明显相关(r=0.256,P<0.05)。P-selectin的配体PSGL-1在肺腺癌、肺鳞癌和小细胞肺癌中表达呈递减趋势。活化血小板促进肺癌细胞跨膜侵袭;抑制P-selectin与其配体PSGL-1结合,肺癌细胞的侵袭与迁移均受到抑制,同时ITGB3的表达明显降低(P<0.05)。结论:血小板P-selectin水平和原发性肺癌患者血行转移之间存在明显相关性,这与P-selectin和配体PSGL-1的结合有关,两者配对后ITGB3水平增加可能是肺癌突破细胞外基质实现血行转移的分子机制之一。
AIM: To investigate the relationship between platelets/P-selectin on activated platelets and clinico-pathological features, hematogenous metastasis and prognosis of lung cancer, and to explore the effect of P-selectin and P-selectin glycoprotein ligand-1(PSGL-1) interaction on the hematogenous metastasis-related integrin β3(ITGB3). METHODS: The expression of P-selectin on activated platelets was detected by flow cytometry, and its effects on lung cancer and the risk of hematogenous metastasis were analyzed. The expression of PSGL-1 in different types of lung cancer tissues and cell lines was determined by Western blot. By co-culturing platelets and lung cancer cells in vitro, the effects of up-and down-regulation of PSGL-1 on invasion and migration abilities of lung cancer cells were observed. RESULTS: The peripheral blood platelet counts and P-selectin expression on activated platelets in the patients with lung cancer were significantly increased(P<0.05). The P-selectin expression on activated platelets was significantly associated with hematogenous metastasis of lung cancer(r=0.256, P<0.05). The strongest expression of PSGL-1 was found in the lung adenocarcinoma samples, next in the lung squamous-cell carcinoma samples, and the weakest in small-cell lung cancer samples. P-selectin promoted transmembrane invasion of lung cancer cells. Inhibition of P-selectin and its ligand PSGL-1 reduced ITGB3 expression, invasion and migration of lung cancer cells. CONCLUSION: The P-selectin level on activated platelets is significantly associated with hematogenous metastasis of lung cancer, which is related to the binding of P-selectin and its ligand PSGL-1. Up-regulation of ITGB3 level after their binding might be one of the mechanisms of the remodeling of extracellular matrix to facilitate hematogenous metastasis of lung cancer.
作者
王倩
朱建兵
吴承高
邹娟
李松
胡飘萍
乐爱平
WANG Qian;ZHU Jian-bing;WU Cheng-gao;ZOU Juan;LI Song;HU Piao-ping;LE Ai-ping(Department of Blood Transfusion,The First Affiliated Hospital of Nanchang University,Nanchang 330006,China;Department of Cardiology,The First Affiliated Hospital of Nanchang University,Nanchang 330006,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2019年第11期1988-1993,共6页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81760381
No.81800324)
江西省教育厅科学技术研究项目(No.GJJ170136
No.GJJ170005)
江西省科技厅青年基金项目(No.20192BAB215047)
