Human endometrial mesenchymal stem cells exhibit intrinsic anti-tumor properties on human epithelial ovarian cancer cells.

Shixia Bu,Qian Wang,Charlie Xiang,Junyan Sun,Zhiwei Liu,Biwei He,Qiuwan Zhang,Dongmei Lai

doi:10.1038/srep37019

Abstract

Epithelial ovarian cancer (EOC) is the most lethal tumor of all gynecologic tumors. There is no curative therapy for EOC thus far. The tumor-homing ability of adult mesenchymal stem cells (MSCs) provide the promising potential to use them as vehicles to transport therapeutic agents to the site of tumor. Meanwhile, studies have showed the intrinsic anti-tumor properties of MSCs against various kinds of cancer, including epithelial ovarian cancer. Human endometrial mesenchymal stem cells (EnSCs) derived from menstrual blood are a novel source for adult MSCs and exert restorative function in some diseases. Whether EnSCs endow innate anti-tumor properties on EOC cells has never been reported. By using tumor-bearing animal model and ex vivo experiments, we found that EnSCs attenuated tumor growth by inducing cell cycle arrest, promoting apoptosis, disturbing mitochondria membrane potential and decreasing pro-angiogenic ability in EOC cells in vitro and/or in vivo. Furthermore, EnSCs decreased AKT phosphorylation and promoted nuclear translocation of Forkhead box O-3a (FoxO3a) in EOC cells. Collectively, our findings elucidated the potential intrinsic anti-tumor properties of EnSCs on EOC cells in vivo and in vitro. This research provides a potential strategy for EnSC-based anti-cancer therapy against epithelial ovarian cancer.

Highlights

Chemotherapy-induced premature ovarian failure/insufficiency[12]
To test whether the anti-tumor properties of EnSCs are specific, not owning to the rapid growth of EnSC-induced exhaustion of trophic factors, we tested the impacts of EnSCs conditioned medium (EnSC-CM) on non-malignant cells and the effects of conditioned medium collected from non-malignant cells on Epithelial ovarian cancer (EOC) cells
We used transwell system to test the effects of EnSCs secretions on EOC cells, in which EnSC-secreted factors could go through transwell membrane and act on cancer cells

Summary

Introduction

Chemotherapy-induced premature ovarian failure/insufficiency[12]. Whether EnSCs endow intrinsic anti-tumor properties on cancer including epithelial ovarian cancer has never been reported before. We established a tumor-bearing mouse model by subcutaneous co-injection of EOC cell line SK-OV-3 and EnSCs. we used EnSCs conditioned medium (EnSC-CM) or transwell system to evaluate their effects on the biological behavior of EOC cells in vitro, including cell viability, cell cycle progression, regulation of mitochondrial membrane potential (MMP), and apoptosis of EOC cells. We elucidated whether EnSCs exerted anti-tumor properties through affecting AKT/Forkhead box O3a (FoxO3a) axis in EOC cells

Methods

Results

Conclusion