活化血小板表面的P-选择素对肺癌血行转移的影响  

P-selectin on activated platelets promotes hematogenous metastasis of primary lung cancer via P-selectin glycoprotein ligand-1

作　　者：王倩[1] 朱建兵 吴承高[1] 邹娟[1] 李松[1] 胡飘萍[1] 乐爱平[1] 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)

机构地区：[1]南昌大学第一附属医院输血科,江西南昌330006 [2]南昌大学第一附属医院心内科,江西南昌330006

出　　处：《中国病理生理杂志》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)

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.

关 键 词：血小板 肺癌 血行转移 P-选择素 P-选择素糖蛋白配体1 整合素Β3 

分 类 号：R730.23[医药卫生—肿瘤] R734.2[医药卫生—临床医学]