title: B7-H4 promotes tumor growth and metastatic progression in lung cancer by impacting cell proliferation and survival.
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.
authors.affiliation: 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.
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, The Affiliated Hospital of Jiangnan University (WuXi No.4 People's Hospital), Wuxi 214000, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Cai
authors.affiliation: Clinical Immunology Laboratory of Jiangsu Province, Suzhou 215006, China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Clinical Immunology Laboratory of Jiangsu Province, Suzhou 215006, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.|Clinical Immunology Laboratory of Jiangsu Province, Suzhou 215006, China.
authors.forename: Jianan
authors.initials: J
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D049109:Cell Proliferation / Q000502:physiology; D018450:Disease Progression; D005260:Female; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D016133:Polymerase Chain Reaction; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000378:metabolism*
chemical_list: D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human
keywords: B7-H4; lung cancer; metastasis; tumorigenesis