Differential role of gonadotropin-releasing hormone on human ovarian epithelial cancer cell invasion.
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.
Chen
Chien-Lin
CL
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taiwan, China.
Cheung
Lydia W T
LW
Lau
Man-Tat
MT
Choi
Jung-Hye
JH
Auersperg
Nelly
N
Wang
Hsin-Shih
HS
Wong
Alice S T
AS
Leung
Peter C K
PC
D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020033:Protein Isoforms; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism
D020033:Protein Isoforms; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D019869:Phosphatidylinositol 3-Kinases; D020778:Matrix Metalloproteinase 2