Gonadotropins promote human ovarian cancer cell migration and invasion via a cyclooxygenase 2-dependent pathway

It is generally accepted that ovarian cancer is associated with local elevation of gonadotropins (FSH and LH), with repeated ovulation and accompanying expression of inducible cyclooxygenase 2 (COX2). However, the roles of gonadotropins and the concomitant elevation of COX2 in the development of ovarian cancer have not, been fully characterized. Herein, we report that excessive FSH/LH exposure did not induce proliferation in ovarian cancer cell lines but significantly promoted cell migration and invasion. Moreover, FSH/LH treatment rapidly upregulated COX2 expression within 24 h, whereas COX1 expression remained unchanged. Further results showed that enhancement of epithelial-mesenchymal transition (EMT) and upregulation of matrix metalloproteinase (MMP)2 and MMP9 contributed to the stimulatory effect of gonadotropins on cell migration and invasion; these effects were sufficiently blocked by a selective COX2 inhibitor. In conclusion, the present study suggests that gonadotropin-induced migration and invasion in ovarian cancer may be caused by EMT and MMP upregulation via a COX2-dependent pathway.