B7-H3促进胃癌细胞的迁移和侵袭。
B7-H3 promotes gastric cancer cell migration and invasion.
作者信息
Li Yecheng, Yang Xiaodong, Wu Yong, Zhao Kui, Ye Zhenyu, Zhu Junjia, Xu Xiaohui, Zhao Xin, Xing Chungen
机构信息
Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, P. R. China.
Department of General Surgery, First Affiliated Hospital of Soochow University, Suzhou, 215006, P.R. China.
出版信息
Oncotarget. 2017 May 13;8(42):71725-71735. doi: 10.18632/oncotarget.17847. eCollection 2017 Sep 22.
B7-H3 (B7 homologue 3, CD276) is a member of the B7 immunoregulatory family and promotes tumor progression. The present study demonstrated that B7-H3 promotes gastric cancer cell migration and invasion. shRNA-mediated B7-H3 silencing in the N87 gastric cancer cell line suppressed cell migration and invasion and ; downregulated metastasis-associated CXCR4; and inhibited AKT, ERK, and Jak2/Stat3 phosphorylation. B7-H3-silenced cells injected into the tail veins of 4-week-old female BALB/c nude mice produced fewer metastases than control cells, and resulted in longer survival times. Immunofluorescence analyses confirmed B7-H3/CXCR4 colocalization in N87 cells, and co-immunoprecipitation assays showed a direct interaction between the two proteins. Our analysis of 120 tissue samples from gastric cancer patients showed that increased B7-H3 expression correlated positively with both tumor infiltration depth and CXCR4 expression. These findings suggest that B7-H3 and CXCR4 may be novel targets for anti-gastric cancer therapeutics.
B7-H3（B7同源物3，CD276）是B7免疫调节家族的成员，可促进肿瘤进展。本研究表明，B7-H3促进胃癌细胞的迁移和侵袭。在N87胃癌细胞系中，通过短发夹RNA（shRNA）介导的B7-H3沉默可抑制细胞迁移和侵袭；下调与转移相关的CXCR4；并抑制AKT、ERK和Jak2/Stat3磷酸化。将B7-H3沉默的细胞注射到4周龄雌性BALB/c裸鼠的尾静脉中，其产生的转移灶比对照细胞少，且存活时间更长。免疫荧光分析证实N87细胞中B7-H3/CXCR4共定位，免疫共沉淀试验表明这两种蛋白之间存在直接相互作用。我们对120例胃癌患者组织样本的分析表明，B7-H3表达增加与肿瘤浸润深度和CXCR4表达均呈正相关。这些发现表明，B7-H3和CXCR4可能是抗胃癌治疗的新靶点。
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