Differential role of gonadotropin-releasing hormone on human ovarian epithelial cancer cell invasion

Endocrine. 2007 Jun;31(3):311-20. doi: 10.1007/s12020-007-0041-8.


Ovarian cancer is the most lethal of all gynecological cancers. Most deaths from ovarian cancer are due to widespread intraperitoneal metastases and malignant ascites. However, mechanisms of invasion in ovarian cancer remain poorly understood. In this study, we examined the effects of gonadotropin-releasing hormone (GnRH)-I (the classical mammalian GnRH), GnRH-II (a second form of GnRH), and GnRH receptor on invasion using two human ovarian carcinoma cell lines, OVCAR-3 and SKOV-3. Here we demonstrated that in OVCAR-3, GnRH-I and GnRH-II promoted cell invasion, whereas in SKOV-3, GnRH-I and GnRH-II inhibited cell invasion. Transfection of small interfering RNA to abrogate the gene expression of GnRH receptor reversed GnRH-I and GnRH-II-mediated invasion activities, suggesting that the same receptor, type I GnRH receptor, is essential for the effects of GnRH-I and GnRH-II in both OVCAR-3 and SKOV-3. Treatment of SKOV-3 cells with GnRH-I or GnRH-II resulted in a decrease in matrix metalloproteinase 2 but an increase in tissue inhibitor of metalloproteinase 2 secretions. In addition, we found that GnRH-I and GnRH-II interfered with activation of the phosphatidylinositol-3-kinase/AKT pathway that is well documented to stimulate proteolysis and invasion of ovarian cancer cells. Taken together, these observations suggest that GnRH-I and GnRH-II play key regulatory roles in ovarian tumor cell invasion and extracellular matrix degradation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Extracellular Matrix / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gonadotropin-Releasing Hormone / genetics
  • Gonadotropin-Releasing Hormone / metabolism*
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Neoplasm Invasiveness* / genetics
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Isoforms
  • RNA, Neoplasm
  • RNA, Small Interfering
  • Receptors, LHRH / genetics
  • Receptors, LHRH / metabolism


  • Protein Isoforms
  • RNA, Neoplasm
  • RNA, Small Interfering
  • Receptors, LHRH
  • Gonadotropin-Releasing Hormone
  • Phosphatidylinositol 3-Kinases
  • Matrix Metalloproteinase 2