title: 17β-Estradiol Reverses Leptin-Inducing Ovarian Cancer Cell Migration by the PI3K/Akt Signaling Pathway.
abstract: Accumulating evidence suggests that leptin is expressed at higher levels in obese women and stimulates cell migration in epithelial cancers. However, the biology of ovarian cancer is different from others, mainly due to the production of estrogens because of the involvement of ovarian tissue, which is the main source of estrogens; as a result, the levels are at least 100- to 1000-fold higher than normal circulating levels. Thus, ovarian cancer tissues are exposed to 17β-estradiol, which promotes ovarian cancer cell migration and may modulate the effect of other hormones. Therefore, this study investigated the effects of 17β-estradiol (1 nmol/L) with leptin (1-40 ng/mL) at physiological levels, on the migration of OVCAR-3 and SKOV-3 ovarian cancer cells, and the expression levels and activity of metalloproteinases (MMPs) 2 and 9. Here, we found that leptin stimulated ovarian cancer cell line migration, which is mediated via the expression and activity of MMP-9 in the OVCAR-3 but not in the SKOV-3 cells. After the administration of 17β-estradiol and leptin, we observed antagonistic effects of 17β-estradiol on leptin-induced OVCAR-3 cell migration and MMP-9 expression and activity. Moreover, the antagonistic effect of 17β-estradiol on leptin-induced cancer cell migration was reversed by pretreatment of the cells with the phosphatidylinositol 3-kinase (PI3K) pathway inhibitor. Taken together, our results, for the first time, show that in ovarian cancer cells ObR+/ER+, 17β-estradiol has an antagonistic effect on leptin-induced cell migration as well as MMP-9 expression and activity, which is mediated by the PI3K pathway.
authors.affiliation: Department of Physiology and Toxicology of Reproduction, Chair of Animal Physiology, Institute of Zoology, Jagiellonian University, Krakow, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Hoffmann
authors.affiliation: Department of Physiology and Toxicology of Reproduction, Chair of Animal Physiology, Institute of Zoology, Jagiellonian University, Krakow, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Fiedor
authors.affiliation: Department of Physiology and Toxicology of Reproduction, Chair of Animal Physiology, Institute of Zoology, Jagiellonian University, Krakow, Poland anna.ptak@uj.edu.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Ptak
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D006801:Humans; D020738:Leptin / Q000494:pharmacology* / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D010051:Ovarian Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D020738:Leptin; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D004958:Estradiol; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: 17β-estradiol; OVCAR-3; SKOV-3; leptin; migration