Research Papers:
B7-H3 promotes gastric cancer cell migration and invasion
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Abstract
Yecheng Li1,*, Xiaodong Yang1,*, Yong Wu1,*, Kui Zhao1, Zhenyu Ye1, Junjia Zhu1, Xiaohui Xu1, Xin Zhao2 and Chungen Xing1
1 Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, P. R. China
2Department of General Surgery, First Affiliated Hospital of Soochow University, Suzhou, 215006, P.R. China
*These authors contributed equally to this work
Correspondence to:
Chungen Xing, email: [email protected]
Xin Zhao, email: [email protected]
Keywords: gastric cancer, B7-H3, CXCR4, migration, invasion
Received: February 08, 2017 Accepted: April 27, 2017 Published: May 13, 2017
ABSTRACT
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 in vitro and in vivo; 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.
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