B7-H4 promotes tumor growth and metastatic progression in lung cancer by impacting cell proliferation and survival

// Xiuqin Zhang 1, 3 , Liming Cai 3 , Guangbo Zhang 2 , Yu Shen 2 , Jianan Huang 1, 2 1 Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, China 2 Clinical Immunology Laboratory of Jiangsu Province, Suzhou 215006, China 3 Department of Respiratory Medicine, The Affiliated Hospital of Jiangnan University (WuXi No.4 People's Hospital), Wuxi 214000, China Correspondence to: Jianan Huang, email: huang_jian_an@163.com Keywords: B7-H4, lung cancer, tumorigenesis, metastasis Received: July 22, 2016 Accepted: December 16, 2016 Published: January 03, 2017 ABSTRACT Aberrant expression of B7-H4 occurs across a broad spectrum of human cancers. The aim of this study was to investigate the key role of B7-H4 during tumorigenesis and metastasis of human lung cancer. Our data showed that the shRNA-mediated disruption of B7-H4 markedly inhibited tumor cell proliferation, invasion and migration, increased cell apoptosis and arrested cell cycle at G0/G1. These changes were accompanied by a marked increase in Bax and caspase-3/ caspase-8, but a decrease in Bcl-2, cyclinD1 and activation of AKT. In addition, our shRNA-mediated disruption of B7-H4 led to a marked decrease in tumor growth in the immune-compromised mice. Importantly, B7-H4 was expressed in 53.33% of lung carcinomas from our patient cohort ( n = 90), but not in any of adjacent non-cancerous tissues, according to our IHC analyses. In particular, B7-H4 expression appeared to be associated with lymph node metastasis ( P = 0.008) and TNM stage ( P = 0.012). Taken together, our study demonstrates a strong promoting role of B7-H4 in lung tumor growth, progression and metastasis, and supports its potential as a therapeutic target for the treatment of the disease.