Effects of HCG on human epithelial ovarian cancer vasculogenic mimicry formation in vivo

Abstract

Ovarian cancer is the leading cause of mortality due to gynecological malignancy, and vasculogenic mimicry (VM) formation is correlated with poor prognosis. In a previous study, the present authors observed that human chorionic gonadotropin (HCG) could promote VM formation in three-dimensional OVCAR-3 cell cultures. In order to investigate whether HCG could promote VM formation in ovarian cancer in vivo, the role of OVCAR-3 cells overexpressing or depleted of chorionic gonadotropin, beta polypeptide 5 (CGB5, which is the fifth subunit of β-HCG and was identified as the key part of HCG) were injected into nude mice in the present study, while BeWo cells were used as a positive control. The results demonstrated that overexpressed CGB5 promoted xenografts tumor formation in nude mice, and the results of hematoxylin and eosin and cluster of differentiation (CD)34-periodic acid-Schiff dual staining revealed that CGB5 promoted VM formation. Furthermore, reverse transcription-polymerase chain reaction and immunochemistry staining demonstrated that the expression of the vascular markers CD31, vascular endothelial growth factor and factor VIII was also upregulated in the CGB5-overexpressing xenografts tumors. In addition, the expression of luteinizing hormone receptor (LHR), the receptor of CGB5, was increased in CGB5-overexpressing cells. In conclusion, CGB5 may promote tumor growth and VM formation via activation of the LHR signal transduction pathway, which may support a novel strategy for ovarian cancer therapy.