Human amniotic epithelial cells inhibit growth of epithelial ovarian cancer cells via TGF-β1-mediated cell cycle arrest

Abstract

It is reported that human amniotic epithelial cells (hAECs) endow intrinsic antitumor effects on certain kinds of cancer. This research was designed to evaluate whether hAECs endowed potential anticancer properties on epithelial ovarian cancer (EOC) cells in vivo and in vitro, which has not been reported before. In this study, we established a xenografted BALB/c nude mouse model by subcutaneously co-injecting ovarian cancer cell line, SK-OV-3, and hAECs for 28 days. In ex vivo experiments, CCK-8 cell viability assay, real-time PCR, cell counting assay, cell cycle analysis and immunohistochemistry (IHC) assay were used to detect the effects of hAEC-secreted factors on the proliferation and cell cycle progression of EOC cells. A cytokine array was conducted to detect anticancer-related cytokines released from hAECs. Human recombinant TGF-β1 and TGF-β1 antibody were used to treat EOC cells and analyzed whether TGF-β1 contributed to the cell cycle arrest. Results from in vivo and ex vivo experiments showed that hAEC-secreted factors and rhTGF-β1 decreased proliferation of EOC cells and induced G0/G1 cell cycle arrest in cancer cells, which could be partially reversed by excess TGF-β1 antibody. These data indicate that hAECs endow potential anticancer properties on epithelial ovarian cancer in vivo and in vitro which is partially mediated by hAEC-secreted TGF-β1-induced cell cycle arrest. This study suggests a potential application of hAEC-based therapy against epithelial ovarian cancer.

The Cells and Extracellular Matrix of Human Amniotic Membrane Hinder the Growth and Invasive Potential of Bladder Urothelial Cancer Cells

“…Whether or not hAMSC, skin-derived human fibroblasts and, partially, Saos-2 cells adopt the same mechanism of inhibition of T24 cell proliferation needs to be addressed. Concerning the possible mechanism used by hAM-derived cells, Magatti et al (2012) showed that hAMSC induce cell cycle arrest in hematopoietic and non-hematopoietic cancer cells ( Magatti et al, 2012 ) and Bu et al (2017) demonstrated that hAEC induce cell cycle arrest in epithelial ovarian cancer cells ( Bu et al, 2017 ). In detail, Magatti et al demonstrated that the cell cycle arrest is induced by down-regulation in the expression of positive regulators of the cell cycle (cyclins D2, E1, H; cyclin-dependent kinases-2, -4, -6; mini-chromosome maintenance complex, proliferating cell nuclear antigen) and upregulation of the cell cycle inhibitors (G2 cyclin, CDK inhibitor 1A, CDK inhibitor N2B).…”

“…Altogether, hAMSC resulted in cycle arrest of cancer cells in the G 0 /G 1 phase and prevention of cell cycle progression to S phase (Magatti et al, 2012). Similarly, Bu et al showed that there was an increase in expression of negative regulators of cell cycle progression, namely p16INK4A and p21 and also demonstrated that TGF-β1 secreted from hAEC plays an important role in cell cycle arrest (Bu et al, 2017). Additionally, Niknejad et al have also shown that cell cycle inhibition can be also caused by inhibition of the heat shock protein 90 (HSP90) (Niknejad et al, 2013b).…”

“…The anticancer properties of hAM started gaining recognition in recent years. Magatti et al (2012) and Bu et al (2017) have demonstrated that hAMSC and hAEC induce a cell cycle arrest in the G0/G1 phase in several cancer cell lines. Moreover, several research groups have shown that hAM and its derivatives promote apoptosis in cancer cells and also reduce the viability and affect the metabolism of cancer cells ( Jiao et al, 2012 ; Niknejad et al, 2013b , 2014 ; Mamede et al, 2014 , 2015 , 2016 ; Riedel et al, 2019 ).…”

Human Amniotic Epithelial Stem Cells: A Promising Seed Cell for Clinical Applications

“…Mechanistically, the expression of telomerase hTERT in hAESCs is not detected, explaining why hAESCs do not generate tumors. Notably, several studies demonstrated that hAESCs could inhibit tumor cell growth and induce apoptosis of cancer cells, including HeLa cells and breast and ovarian cancer cells [ 94 , 95 , 96 ]. However, Yang et al reported that co-injection of hAESCs and Raji tumor cells into immunodeficient mice shows a similar survival duration when compared with the mice receiving only Raji cells, which indicated hAESCs have little effect on tumor growth [ 29 ].…”

Application of Dried Human Amnion Graft to Improve Post-Prostatectomy Incontinence and Potency: A Randomized Exploration Study Protocol

“…Several studies have indicated that HAM might display anticancer activity. A suppression of different cancer lines by the addition of HAM in vitro has been shown, but clinical studies are missing [42,43]. In the presented protocol oncologic results are being recorded to assess the biochemical recurrence.…”