title: Roles of immune inhibitory molecule B7-H4 in cervical cancer.
abstract: Recent studies have reported that the immune-regulatory protein B7-H4 is highly expressed in various types of cancer, but little is known concerning its roles in cervical cancer. In the present study, we investigated the expression of B7-H4 in human tissues and serum samples, and explored the effects of B7-H4 on proliferation, apoptosis, migration and invasion of cervical cancer cell lines, including SiHa and HeLa. We found that B7-H4 was mainly located in the cytoplasm of cervical cancer cells as determined by immunofluorescence staining. Serum B7-H4 (sB7-H4) was overexpressed in patients with cervical intraepithelial neoplasia (CIN) and cervical cancer, and the area under the ROC curve (AUC) was 0.955. There was no statistical significance between B7-H4 expression and clinicopathological factors in cervical cancer tissue samples. B7-H4 promoted the proliferation of SiHa and HeLa cells, and protected them from apoptosis, which was related to the upregulation of E7, phosphorylated Rb (pRb), E2F, P16, P21, Bcl-2 and the downregulation of Rb, cleaved PARP and cleaved caspase-3 as determined by western blotting. In addition, B7-H4 increased the ability of cell migration and invasion by targeting angiogenic factors, matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF) as determined by RT-PCR. Our findings revealed that B7-H4 has the potential to be a useful prognostic marker. In addition, B7-H4 plays important roles in proliferation, apoptosis, migration and invasion, indicating that B7-H4 can serve as a new therapeutic target for cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Sai
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Qian
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Youzhong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000235:genetics* / Q000378:metabolism*; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human