Abstract
BackgroundHuman chorionic gonadotropin (hCG) can play a crucial role in angiogenesis. In the present study, we focused on hCG to gain insight into its potential effects on vasculogenic mimicry (VM) in ovarian cancer cells.MethodsOvarian cancer OVCAR-3 cells were incubated with different concentrations of recombinant hCG in 3-dimensional cultures. VM was identified by morphological observations and vascular endothelial cell marker detection in OVCAR-3 cells. Expression of hCG, hypoxia-inducible factor-1α (HIF-1α), and the endothelial cell markers CD31, VEGF, and factor VIII were detected by reverse transcription polymerase chain reaction and western blotting. The effect of hCG on endothelial cell-marker expression in ovarian cancer cells was further explored using small interfering RNA (siRNA) and plasmid-based approaches.ResultsIncubation of OVCAR-3 cells with recombinant hCG induced vessel-like network formation, which was accompanied by significant elevation of vascular marker expression. Attenuation of hCG expression by siRNA in OVCAR-3 cells suppressed the expression of endothelial cell markers and HIF-1α by tumour cells. Overexpression of hCG in OVCAR-3 cells resulted in increased expression of endothelial cell markers and HIF-1α.ConclusionsHCG was crucial for changing the phenotype of OVCAR-3 cells to endothelial-like cells. The effect of hCG induction on VM in ovarian cancer cells is potentially associated with HIF-1α.
Highlights
Human chorionic gonadotropin can play a crucial role in angiogenesis
We explored the possible effects of Human chorionic gonadotropin (hCG) on vasculogenic mimicry (VM) in the hCG receptor-positive ovarian cancer cell line OVCAR-3 in a 3D angiogenesis system
We found that the relative expression of hCG in OVCAR-3 cells significantly increased in response to hCG treatment in a dose-dependent manner, compared with that observed in unstimulated cells (Fig. 1a–d)
Summary
We focused on hCG to gain insight into its potential effects on vasculogenic mimicry (VM) in ovarian cancer cells. Tumour cells have direct access to the bloodstream through the tumour cell-lined vessels and tend to Choriocarcinoma, which is noted to have high-level human chorionic gonadotropin (hCG) production, is characterized by the presence of a multitude of. We reported that ovarian cancer cells can express endothelium-associated genes to form vasculogenic-like networks in 3D gels in a microenvironment containing added hCG [12, 13]. Produced hCG has recently been found to exhibit angiogenic growth factor properties that are central to cancer progression [16]. Β-HCG expression in cervical cancer is associated with the extent of tumour vascularisation [21]. Serum hCG levels have recently been linked to neo-vascularisation of non-seminomatous testicular germ cell tumours [22]. Little has been reported regarding the effects of hCG on VM
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