Suppression of migratory/invasive ability and induction of apoptosis in adenomyosis-derived mesenchymal stem cells by cyclooxygenase-2 inhibitors

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Cyclooxygenase-2 inhibitors suppress the migratory and invasive abilities of adenomyosis-derived mesenchymal stem cells while inducing apoptosis.

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Abstract

ObjectiveTo investigate if stem or progenitor cells are found in adenomyosis and to characterize the role of cyclooxygenase-2 (COX-2) in adenomyosis-derived mesenchymal stem cell (AMSC)-related pathogenesis of adenomyosis.DesignExperimental clinical study.SettingUniversity hospital.Patient(s)Ten patients with adenomyosis.Intervention(s)Hysterectomy.Main outcome measure(s)The gene expression of AMSCs and endometrial mesenchymal stem cells (EMSCs) were analyzed by microarray, quantitative polymerase chain reaction and Western blot. Methylthiazol tetrazolium, proliferation, apoptosis, and migration/invasion assays of AMSCs and EMSCs were evaluated after COX-2 inhibitor treatment.Result(s)We isolated nine EMSCs from normal endometrium (n=10) and six AMSCs (n=10) from adenomyosis. The morphology, phenotype, and potential of multilineage differentiation between EMSCs and AMSCs were not significantly different. Using complementary DNA microarrays, the expression profiles of EMSCs are related to those of bone marrow-derived mesenchymal stem cells (BMSCs), but AMSCs are different from EMSCs and BMSCs in the gene profiles. We validated the microarray results and showed that there is increased COX-2 expression in AMSCs compared with EMSCs. Treatment with a COX-2 inhibitor suppressed migration and invasion and induced apoptotic capabilities of AMSCs, but not of EMSCs.Conclusion(s)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.

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Condition tags

endometriosisadenomyosis

MeSH descriptors

Apoptosis Cell Movement Cyclooxygenase 2 Inhibitors Endometriosis Mesenchymal Stem Cells Uterine Diseases Adult Apoptosis Apoptosis Cell Adhesion Cell Adhesion Cell Adhesion Cell Movement Cell Movement Cell Movement Cells, Cultured Cyclooxygenase 2 Inhibitors Down-Regulation Down-Regulation Down-Regulation

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