title: Elevated phosphatase of regenerating liver 3 (PRL-3) promotes cytoskeleton reorganization, cell migration and invasion in endometrial stromal cells from endometrioma.
abstract: OBJECTIVE
  Is phosphatase of regenerating liver-3 (PRL-3) associated with increased motility of endometriotic cells from endometrioma?
  
  
  CONCLUSIONS
  Elevated PRL-3 promotes cytoskeleton reorganization, cell migration and invasion of endometrial stromal cells (ESCs) from endometrioma.
  
  
  BACKGROUND
  Overexpression of PRL-3 is associated with cancer cell migration, invasion and metastatic phenotype.
  
  
  METHODS
  Primary human ESCs were isolated from eutopic endometrium of women without endometriosis (EuCo, n = 10), with histologically proven endometrioma (EuEM, n = 19) and from the cyst wall of ovarian endometriosis (OvEM, n = 26).
  
  
  METHODS
  The expression of PRL-3 in ESCs derived from EuCo, EuEM and OvEM at different phases of menstrual cycle were compared. The protein and mRNA levels of PRL-3 were examined by western blot and RT-qPCR, respectively. ESCs from OvEM were transfected with/without short hairpin RNA (shRNA) or small interfering RNA (siRNA). Additionally, a plasmid-mediated delivery system was used to achieve PRL-3 overexpression in ESCs from EuEM. The cellular distribution of F-actin and α-tubulin were examined by immunocytochemistry. Cell motility was evaluated by a transwell migration/invasion assay.
  
  
  RESULTS
  The protein and mRNA levels of PRL-3 are significantly elevated in ESCs from OvEM compared with EuCo and EuEM. The expression of PRL-3 was not altered between proliferative phase and secretory phase in ESCs from all groups. Knockdown of PRL-3 significantly modified the distribution of F-actin and α-tubulin cytoskeleton, inhibited cell migration and invasion. Endogenous inhibition of PRL-3 attenuated the expression of Ras homolog gene family members A and C (RhoA, RhoC), Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) and matrix metalloproteinase (MMP) 9, but not MMP2 in ESCs from OvEM. Additionally, overexpression of PRL-3 in ESCs from EuEM up-regulates cell migration and invasion, and increases the expression of RhoA, RhoC, ROCK1 and MMP9.
  
  
  CONCLUSIONS
  Lack of in vivo animal studies is the major limitation of our report. Our results should be further confirmed in a larger cohort of patients and extended to include eutopic and ectopic endometrium from patients with peritoneal endometriosis at different stages of the disease.
  
  
  CONCLUSIONS
  Our study describes that elevated expression of PRL-3 contributes to the cell motility of ESCs from endometrioma. The results emphasize the importance of metastatic-related factor PRL-3 in the pathogenesis of endometrioma.
  
  
  BACKGROUND
  This work was supported by National Natural Science Foundation of China (No. 81170546) and Zhejiang Medicine Science and Technology Projects (No. Y13H040003). The authors declare no conflict of interest.
authors.affiliation: Department of Gynecology and Obstetrics, Women's Hospital, Zhejiang University Medical College, Hangzhou 310006, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhan
authors.affiliation: Department of Gynecology and Obstetrics, Women's Hospital, Zhejiang University Medical College, Hangzhou 310006, P.R. China.
authors.forename: Junyan
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Gynecology and Obstetrics, Women's Hospital, Zhejiang University Medical College, Hangzhou 310006, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ruan
authors.affiliation: Department of Obstetrics & Gynaecology, Child & Family Research Institute, The University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Bedaiwy
authors.affiliation: Department of Obstetrics & Gynaecology, Child & Family Research Institute, The University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4.
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.affiliation: Department of Gynecology and Obstetrics, Women's Hospital, Zhejiang University Medical College, Hangzhou 310006, P.R. China.
authors.forename: Ruijin
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Gynecology and Obstetrics, Women's Hospital, Zhejiang University Medical College, Hangzhou 310006, P.R. China linjun1088@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
mesh_terms: D002465:Cell Movement; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism* / Q000473:pathology; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D004790:Enzyme Induction; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008597:Menstrual Cycle / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010049:Ovarian Diseases / Q000378:metabolism* / Q000473:pathology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D020741:rho GTP-Binding Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000075024:rhoC GTP-Binding Protein
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C066737:RHOA protein, human; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein
keywords: Ras homolog gene family members; Rho-associated coiled-coil-containing protein kinase 1; cytoskeleton; endometrioma; endometriosis; invasion; matrix metalloproteinase; migration; phosphatase of regenerating liver-3