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An HCG-rich microenvironment contributes to ovarian cancer cell differentiation into endothelioid cells in a three-dimensional culture system.
- Source :
-
Oncology reports [Oncol Rep] 2015 Nov; Vol. 34 (5), pp. 2395-402. Date of Electronic Publication: 2015 Aug 20. - Publication Year :
- 2015
-
Abstract
- We investigated the expression of human chorionic gonadotropin (HCG) and its effects on vasculogenic mimicry (VM) formation in ovarian cancer cells under normoxic and hypoxic conditions in three-dimensional matrices preconditioned by an endothelial-trophoblast cell co-culture system. The co-culture model was established using human umbilical vein endothelial cells (HUVECs) and HTR-8 trophoblast cells in a three-dimensional culture system. The co-cultured cells were removed with NH4OH, and ovarian cancer cells were implanted into the preconditioned matrix. VM was identified morphologically and by detecting vascular markers expressed by cancer cells. The specificity of the effects of exogenous HCG in the microenvironment was assessed by inhibition with a neutralizing anti-HCG antibody. HCG siRNA was used to knock down endogenous HCG expression in OVCAR-3 ovarian cancer cells. HTR-8 cells 'fingerprinted' HUVECs to form capillary-like tube structures in co-cultures. In the preconditioned HCG-rich microenvironment, the number of vessel-like network structures formed by HCG receptor-positive OVCAR-3 cells and the expression levels of CD31, VEGF and factor VIII were significantly increased. The preconditioned HCG-rich microenvironment significantly increased the expression of hypoxia inducible factor-1α (HIF‑1α) and VM formation in OVCAR-3 cells under hypoxic conditions. Treatment with a neutralizing anti-HCG antibody but not HCG siRNA significantly inhibited the formation of vessel-like network structures. HCG in the microenvironment contributes to OVCAR-3 differentiation into endothelioid cells in three-dimensional matrices preconditioned with an endothelial-trophoblast cell co-culture system. HCG may synergistically enhance hypoxia-induced vascular markers and HIF-1α expression. These findings would provide perspectives on new therapeutic targets for ovarian cancer.
- Subjects :
- Cell Hypoxia
Cell Line, Tumor
Cell Transformation, Neoplastic
Coculture Techniques
Female
Human Umbilical Vein Endothelial Cells physiology
Humans
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Neovascularization, Pathologic metabolism
Ovarian Neoplasms blood supply
Receptors, LH metabolism
Tumor Microenvironment
Chorionic Gonadotropin physiology
Ovarian Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2431
- Volume :
- 34
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 26479853
- Full Text :
- https://doi.org/10.3892/or.2015.4215