Oncotarget

Research Papers:

B7-H3 promotes gastric cancer cell migration and invasion

Yecheng Li, Xiaodong Yang, Yong Wu, Kui Zhao, Zhenyu Ye, Junjia Zhu, Xiaohui Xu, Xin Zhao and Chungen Xing _

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Oncotarget. 2017; 8:71725-71735. https://doi.org/10.18632/oncotarget.17847

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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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