B7-H4 expression promotes tumorigenesis in ovarian cancer.
BACKGROUND
It has been previously shown that B7-H4, one of the B7 family members that serve as negative regulators of T cell function, has altered expression levels in a variety of cancers, overexpression of B7-H4 promotes cellular transformation. However, there is still lack of adequate evidence to establish a direct connection between B7-H4 expression and malignant transformation.


METHODS
Herein, we constructed pE-green fluorescent protein-N1/B7-H4 mammalian expression vector and transfected into B7-H4-negative human ovarian cancer cell line SKOV3. Cellular proliferation, apoptosis, adhesion, motility, and invasion were examined in vitro. Cells injected subcutaneously into severe combined immunodeficient mouse were analyzed for the possible functions of B7-H4 in ovarian tumorigenesis in vivo.


RESULTS
Fluorescence microscopy studies confirmed that the B7-H4-green fluorescent protein localizes in the cytoplasm of SKOV3/B7-H4 cells, whereas green fluorescent protein is uniformly distributed throughout the cell. B7-H4 promoted cellular proliferation rate and increased cell adhesion, migration, and invasion. In addition, SKOV3 cells expressing B7-H4 gained growth advantage in the xenograft model in vivo.


CONCLUSIONS
These studies demonstrate that B7-H4 directly promotes malignant transformation of ovarian cancer cell line, and provides a potential therapeutic strategy for targeting B7-H4 to inhibit progression of human ovarian cancers.
Cheng
Lei
L
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, P.R. China.
Jiang
Jie
J
Gao
Ran
R
Wei
Shuangyan
S
Nan
Fangfang
F
Li
Shaoru
S
Kong
Beihua
B
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
D018122:B7-1 Antigen; D011993:Recombinant Fusion Proteins; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human; D049452:Green Fluorescent Proteins