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

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.

SUBMITTER: Bu S

PROVIDER: S-EPMC5109482 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

Bu Shixia S Wang Qian Q Zhang Qiuwan Q Sun Junyan J He Biwei B Xiang Charlie C Liu Zhiwei Z Lai Dongmei D

Scientific reports 20161115

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) d ...[more]

PMID: 27845405

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Project description:BackgroundThe biological phenomenon of cell fusion has been associated with cancer progression since it was determined that normal cell × tumor cell fusion-derived hybrid cells could exhibit novel properties, such as enhanced metastatogenic capacity or increased drug resistance, and even as a mechanism that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been proposed as cancer cells that exhibit stem cell properties, including the ability to (re)initiate tumor growth.MethodsFive M13HS hybrid clone cells, which originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human breast epithelial cells and HS578T-Hyg human breast cancer cells, and their parental cells were analyzed for expression of stemness and EMT-related marker proteins by Western blot analysis and confocal laser scanning microscopy. The frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed fluorescent dye. Concurrently, the cells' colony forming capabilities as well as the cells' abilities to form mammospheres were investigated. The migratory activity of the cells was analyzed using a 3D collagen matrix migration assay.ResultsM13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which were differently expressed in parental cells. A variation in the ALDH1-positive putative stem cell population was observed among the five hybrids ranging from 1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all five hybrid clone cells possessed increased but also unique colony formation and mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the highest colony formation capacity and second highest mammosphere formation capacity of all hybrids, whereby the mean diameter of the mammospheres was comparable to the parental cells. In contrast, the largest mammospheres originated from the M13HS-2 hybrid clone cells, whereas these cells' mammosphere formation capacity was comparable to the parental breast cancer cells. All M13HS hybrid clones exhibited a mesenchymal phenotype and, with the exception of one hybrid clone, responded to EGF with an increased migratory activity.ConclusionFusion of human breast epithelial cells and human breast cancer cells can give rise to hybrid clone cells that possess certain CS/IC properties, suggesting that cell fusion might be a mechanism underlying how tumor cells exhibiting a CS/IC phenotype could originate.

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

Publications

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

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