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Oncotarget. 2017 Mar 21;8(12):18861-18871. doi: 10.18632/oncotarget.14475.

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

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Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Department of Respiratory Medicine, The Affiliated Hospital of Jiangnan University (WuXi No.4 People's Hospital), Wuxi 214000, China.
Clinical Immunology Laboratory of Jiangsu Province, Suzhou 215006, China.


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.


B7-H4; lung cancer; metastasis; tumorigenesis

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