The Study of Endometrial Mesenchymal Stem Cells in Gynecological Tumor

• Main Authors: Yi-Jen Chen, 陳怡仁
• Other Authors: Chiou-Chung Yuan
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/99538057200641979475

博士 === 國立陽明大學 === 臨床醫學研究所 === 98 === Suppression of Migratory/invasive Ability and Induction of Apoptosis in Adenomyosis-derived Mesenchymal Stem Cells by Cyclooxygenase-2 Inhibitors Stem cells are undifferentiated cells that are defined by their ability, at the single cell level, to both self-renew and differentiate into mature cells. Recent studies showed that the human endometrium contains a population of stem cells that is responsible for its remarkable ability to regenerate. Adenomyosis is defined by the presence of endometrial glandular tissues of great than 2.5 mm that extends below the endometrial-myometrial interface and is a common gynecological disorder affecting 8-62 % of women of reproductive age. Symptoms of adenomyosis include heavy menstrual bleeding, dyspareunia and dysmenorrhea. Adenomyosis is associated with abnormal endometrial proliferation, so the role of endometrial stem/progenitor cells in the pathophysiology of adenomyosis require further investigation. Cyclooxygenase-2 (COX-2), the enzyme that converts arachidonic acid into prostaglandins (PGs), is overexpressed in endometriotic lesions compared to eutopic endometrium. COX-2 is related to the characteristics of adenomyotic cells. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit COX enzymes and consequently prevent, inhibit, or abolish the effects of PGs. Interestingly, the selective inhibition of COX-2 was shown to reduce pelvic pain that was associated with adenomyosis. These results showed that COX-2 promotes the pathophysiology and pathogenesis of adenomyosis. However, the expression of COX-2 in endometrial stem cells and Adenomyosis-derived Mesenchymal Stem Cells (AMSCs) is still unknown. We isolated nine EMSCs from normal endometrium (n=10) and six AMSCs (n=10) from adenomyosis. The morphology, phenotype and potential of multi-lineage differentiation between EMSCs and AMSCs were not significantly different. Using cDNA microarrays, the expression profiles of EMSCs are related to those of BMSCs, but AMSCs are different to EMSCs and BMSCs in the gene profiles. We validated the microarray results and show that there is increased COX-2 expression in AMSCs compared to EMSCs. Treatment with a COX-2 inhibitor suppressed migration and invasion, and induced apoptotic capabilities of AMSCs, but not EMSCs. Overexpression of COX-2 in AMSCs may play an important role in the pathogenesis of adenomyosis. COX-2 could be a possible target for treatment and prevention of adenomyosis.