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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.

Author information

1
Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
2
Department of Respiratory Medicine, The Affiliated Hospital of Jiangnan University (WuXi No.4 People's Hospital), Wuxi 214000, China.
3
Clinical Immunology Laboratory of Jiangsu Province, Suzhou 215006, China.

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.

KEYWORDS:

B7-H4; lung cancer; metastasis; tumorigenesis

PMID:
28061481
PMCID:
PMC5386653
DOI:
10.18632/oncotarget.14475
[Indexed for MEDLINE]
Free PMC Article

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