Epithelial ovarian cancer (EOC) cells express Wnt5a, but its role in ovarian cancer progression is poorly defined. The aims of the present study were two-fold: 1) to determine the Wnt5a role in viability, apoptosis, migration, colony formation and adhesion of human serous epithelial ovarian cancer cell line SKOV-3, and 2) to assess the relationship of Wnt5a with E- and N-cadherin in high- and low-grade human serous ovarian cancer specimens. Wnt5a over-expression led to 29% increased serum-independent cell viability (P < 0.05) and 35% decreased caspase-3 activity (P < 0.01) compared to SKOV-3 cells. There was 96% (P < 0.001) increased cell motility in Wnt5a-transfected SKOV-3 (SKOV-3/Wnt5a) cells compared to SKOV-3, which was abrogated in the presence of JNK inhibitor. In addition, there was about 42% increased cell adhesion to Matrigel compared to SKOV-3 cells (P < 0.001). Colony-forming assay showed a 4.4-fold increased colony formation in SKOV-3/Wnt5a cells compared to SKOV-3 cells (P < 0.001). E- and N-cadherin levels were reduced by 49 % and 67 % in SKOV-3/Wnt5a cells compared to mock cells, respectively. Wnt5a and E-cadherin immunoexpression was significantly (P < 0.001) different in low-grade serous ovarian cancer (LGSC) and high-grade serous ovarian cancer (HGSC). In HGSC specimens, strong immunoexpression of Wnt5a was detected compared to LGSC. However, E-cadherin showed moderate immunostaining (84 %) in HGSC, whereas 100 % of LGSC specimens showed strong immunoexpression. In both groups no N-cadherin immunoexpression was detected. Moreover, Wnt5a showed a positive relationship with E-cadherin in the LGSC group (r = 0.661, P = 0.027). These results may support important roles for Wnt5a in EOC progression.

Department of Animal Physiology Developmental Biology Laboratory School of Biology University College of Science University of Tehran Tehran Iran

Department of Pathology Women's Hospital Tehran University of Medical Sciences Tehran Iran