Wnt5a influences viability, migration, adhesion, colony formation, E- and N-cadherin expression of human ovarian...

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.