Modulation of tumor stem cell characteristics by 17β-estradiol in human mesenchymal stem cells derived from ovarian endometrioma

Abstract

Objective: Ovarian endometrioma is a cyst composed of endometrial tissue and is present in 20%–40% of patients with endometriosis. Endometriosis is an estrogen-dependent benign and chronic gynecological disease that affects women of reproductive age. Studies have reported that tumor stem cells can be isolated from numerous tumor types. Emerging evidence has indicated that tumor stem cells may be responsible for the development of endometriosis and endometrial tumors. The present study investigated the effects of 17β-estradiol on levels of expression of stem cell markers and cell growth of human mesenchymal stem cells derived from ovarian endometrioma (hOVEN-MSCs). Materials and methods: hOVEN-MSCs were isolated from human ovarian endometrioma. The proliferation potential of hOVEN-MSCs was measured by the cumulative population doubling and colony-formation efficiency. The gene expression of the hOVEN-MSCs was examined by the reverse transcription-polymerase chain reaction analysis. Protein expression assays were performed using flow cytometry and western blot analysis. Results: This study demonstrated that hOVEN-MSCs can be isolated from ovarian endometrioma and that 17β-estradiol was capable of increasing colony-forming efficiency and cell proliferation of these cells. In addition, we found that 17β-estradiol not only increased the expression of the stem cell marker OCT-4, but also increased the expression of endometrial tumor stem cell markers CD133 and ALDH1 in hOVEN-MSCs. Conclusion: The above results indicate an important role of 17β-estradiol in cell growth of hOVEN-MSCs concomitant with enhanced expression of stem cell markers. This effect of 17β-estradiol related to stem cell marker expression, if confirmed by further in vitro, in vivo studies, may be useful for developing new strategies for prevention and treatment of endometriosis and endometrioma. Keywords: 17β-estradiol, ALDH1, CD133, OCT-4, Tumor stem cells