An HCG-rich microenvironment contributes to ovarian cancer cell differentiation into endothelioid cells in a three-dimensional culture system

  • Authors:
    • Min Su
    • Chao Fan
    • Sainan Gao
    • Aiguo Shen
    • Xiaoying Wang
    • Yuquan Zhang
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  • Published online on: August 20, 2015     https://doi.org/10.3892/or.2015.4215
  • Pages: 2395-2402
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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.
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November-2015
Volume 34 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Su M, Fan C, Gao S, Shen A, Wang X and Zhang Y: An HCG-rich microenvironment contributes to ovarian cancer cell differentiation into endothelioid cells in a three-dimensional culture system. Oncol Rep 34: 2395-2402, 2015
APA
Su, M., Fan, C., Gao, S., Shen, A., Wang, X., & Zhang, Y. (2015). An HCG-rich microenvironment contributes to ovarian cancer cell differentiation into endothelioid cells in a three-dimensional culture system. Oncology Reports, 34, 2395-2402. https://doi.org/10.3892/or.2015.4215
MLA
Su, M., Fan, C., Gao, S., Shen, A., Wang, X., Zhang, Y."An HCG-rich microenvironment contributes to ovarian cancer cell differentiation into endothelioid cells in a three-dimensional culture system". Oncology Reports 34.5 (2015): 2395-2402.
Chicago
Su, M., Fan, C., Gao, S., Shen, A., Wang, X., Zhang, Y."An HCG-rich microenvironment contributes to ovarian cancer cell differentiation into endothelioid cells in a three-dimensional culture system". Oncology Reports 34, no. 5 (2015): 2395-2402. https://doi.org/10.3892/or.2015.4215