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


METHODS
Experimental clinical study.


METHODS
University hospital.


METHODS
Ten patients with adenomyosis.


METHODS
Hysterectomy.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Institute of Clinical Medicin, National Yang-Ming University, Taipei, Taiwan.
Yi-Jen
YJ
Chen
Hsin-Yang
HY
Li
Yuh-Lih
YL
Chang
Chiou-Chung
CC
Yuan
Lung-Kuo
LK
Tai
Kai Hsi
KH
Lu
Chia-Ming
CM
Chang
Shih-Hwa
SH
Chiou
D000328:Adult; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008875:Middle Aged; D009578:Nitrobenzenes / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D014591:Uterine Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide