B7-H3 promotes gastric cancer cell migration and invasion

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

doi:10.18632/oncotarget.17847

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.

Highlights

Gastric cancer is the fourth most frequently diagnosed cancer and the second most common cause of cancer-related deaths worldwide [1]
The present study demonstrated that B7-H3 promotes gastric cancer cell migration and invasion. small hairpin RNA (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 expression in gastric cancer was not correlated with patient age, sex, lymph node metastasis, degree of differentiation, or HER-2 status

Summary

Introduction

Gastric cancer is the fourth most frequently diagnosed cancer and the second most common cause of cancer-related deaths worldwide [1]. Improved diagnostic and therapeutic strategies have improved early-stage gastric cancer detection and decreased patient mortality [2]. New anticancer agents, such as S-1, tananes, capecitabine, oxaliplatin, and irinotecan [3,4,5,6,7], have improved gastric cancer patient prognoses, survival rates remain unsatisfactory [8, 9]. B7H3 reportedly both activates and inhibits T cell responses [15, 16], and may promote disease progression in pancreatic carcinoma [17], hepatocellular cancer [18], human esophageal cancer [19], non-small cell lung cancer [20], prostate cancer [21], endometrial cancer [22], and gastric cancer [2]. B7-H3 studies in gastric cancer produced conflicting results [23], and the B7-H3 mechanism of action in malignant tumors remains unclear

Methods

Results

Conclusion