趋化因子受体CXCR7通过VEGF促进胃癌生长  

Chemokine receptor CXCR7 promotes gastric cancer growth via VEGF

作　　者：辛琪[1] 张娜 温丽坤[1] 张勤[1] 张传山[1] Qi Xin;Na Zhang;Li-Kun Wen;Qin Zhang;Chuan-Shan Zhang(Tianjin Third Central Hospital, Tianjin Research Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cells, Research Center of Artificial Cell Engineering Technology of the Ministry of Health, Tianjin 300170, China)

机构地区：[1]天津市第三中心医院天津市肝胆疾病研究所天津市人工细胞重点实验室卫生部人工细胞工程技术研究中心,天津市300170 [2]天津市滨海新区大港医院病理科,天津市300270

出　　处：《世界华人消化杂志》2018年第11期639-647,共9页World Chinese Journal of Digestology

基　　金：天津市第三中心医院国家自然科学基金孵育项目;No.2017YNY3;天津市滨海新区科技发展战略研究计划项目;No.2012DK15W007;天津市滨海新区卫生和计划生育委员会科技项目;No.2017BWKY022~~

摘　　要：目的探讨CXCR7对人胃癌细胞株SGC-7901生长的影响,并研究阻断CXCR7对胃癌肿瘤生长的影响.方法利用RNA重组质粒技术,构建CXCR7的si RNA慢病毒表达载体,转染人胃癌细胞株SGC-7901,评价沉默CXCR7的SGC-7901细胞在黏附、侵袭、血管内皮生长因子(vascular endothelial growth factor,VEGF)的分泌及血管新生方面的影响;运用免疫组化和免疫荧光双染检测人胃癌组织中CXCR7在血管内皮的表达情况;同时运用动物实验靶向抑制CXCR7检测对胃癌生长的影响,运用CD31染色显示肿瘤新生血管,揭示CXCR7与血管密度的关系,同时运用PCR检测VEGF的含量.结果在体外,CXCR7促进SGC-7901细胞的黏附、侵袭和VEGF的分泌;免疫组化和免疫荧光双染显示CXCR7能够表达在人胃癌组织的血管内皮细胞上;在鼠体内,CXCR7的阻滞剂CCX711能够抑制肿瘤的生长(体积F=5.487,P=0.047;重量F=5.364,P=0.049)和血管新生(F=6.438,P=0.035)并能够减少VEGF的分泌(F=87.211,P=0.000).结论 CXCR7能够促进胃癌细胞SGC-7901的黏附、侵袭和血管新生,靶向阻滞CXCR7可以减少血管新生,阻止胃癌的生长,为胃癌的治疗提供一个潜在的作用靶点.AIM To investigate the ettect of CXCR7 on rne invasion, of human gastric cancer cell line SGC-7901, and to explore the effect of blocking CXCR7 on gastric cancer growth and the underlying molecular mechanism.A lentiviral vector overexpressing CXCR7 was transfected into SGC-7901 cells, and RT-PCR and Western blot were used to confirm if transfection was successful. The effect of CXCR7 overexpression on cell invasion and adhesion as well as vascular endothelial growth factor （VEGF） secretion was also assessed. Immunohistochemistry and immunofluorescence double staining were performed to assess the expression of CXCR7 in the vascular endothelium of human gastric cancer tissues. After blocking CXCR7 in nude mice carrying tumors, new blood vessels were detected by immunohistochemical staining for CD31 and microvessel density was calculated to reveal the relationship between CXCR7 and vascular density. The expression of VEGF was also detected.In vitro, CXCR7 was found to induce cell invasion and adhesion and VEGF secretion in SGC-7901 cells. CXCR7was expressed in blood vessels of human gastric cancer tissues. In vivo, tumor growth （volume： F = 5.487, P = 0.047; weight： F = 5.364, P = 0.049） and angiogenesis （F = 6.438, P = 0.035） were suppressed, and VEGF was down-regulated （F = 87.211, P = 0.000） by CCX711.

关 键 词：胃肿瘤 CXCR7 细胞侵袭 细胞黏附 血管新生 

分 类 号：R735.2[医药卫生—肿瘤]