Elevated phosphatase of regenerating liver 3 (PRL-3) promotes cytoskeleton reorganization, cell migration and invasion in endometrial stromal cells from endometrioma.Hum Reprod 2016; 31(4):723-33HR
Is phosphatase of regenerating liver-3 (PRL-3) associated with increased motility of endometriotic cells from endometrioma?
Elevated PRL-3 promotes cytoskeleton reorganization, cell migration and invasion of endometrial stromal cells (ESCs) from endometrioma.
WHAT IS KNOWN ALREADY
Overexpression of PRL-3 is associated with cancer cell migration, invasion and metastatic phenotype.
STUDY DESIGN, SIZE, DURATION
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).
PARTICIPANTS/MATERIALS, SETTING, 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.
MAIN RESULTS AND THE ROLE OF CHANCE
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.
LIMITATIONS, REASONS FOR CAUTION
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.
WIDER IMPLICATIONS OF THE FINDINGS
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.
STUDY FUNDING/COMPETING INTEREST
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.