Resistin regulates human choriocarcinoma cell invasive behaviour and endothelial cell angiogenic processes.
Resistin is a novel hormone that is secreted by human adipocytes and mononuclear cells and is probably associated with insulin resistance. Recently, resistin has been postulated to play a role in pregnancy, and resistin gene expression has been observed in placental tissues. However, it is still not known if resistin is able to affect trophoblast functions and development. Therefore, we investigated the hypothesis that resistin might regulate trophoblast production of matrix metalloproteinases (MMPs), the tissue inhibitors of metalloproteinases (TIMPs), trophoblast invasive behavior and the angiogenic processes. In human choriocarcinoma cells (BeWo), resistin (10-100 ng/ml) enhanced both MMP-2 protein and mRNA expression, significantly reduced TIMP-1 and TIMP-2 and increased trophoblast-like cell invasiveness. We analyzed the effect of resistin on an in vitro angiogenesis system for endothelial cells (HUVEC) and we evaluated its ability to modulate the secretion of an angiogenic factor, vascular endothelial growth factor (VEGF). Our data showed that resistin induced VEGF production and we observed that the addition of resistin stimulated endothelial cell tube formation. These findings suggest that resistin might be able to induce BeWo cell invasiveness and to contribute to the control of placental vascular development.
Di Simone
Nicoletta
N
Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Largo Gemelli 8, 00168 Rome, Italy. nicoletta.disimone@virgilio.it
Di Nicuolo
Fiorella
F
Sanguinetti
Maurizio
M
Castellani
Roberta
R
D'Asta
Marco
M
Caforio
Leonardo
L
Caruso
Alessandro
A
D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002822:Choriocarcinoma / Q000188:drug therapy / Q000473:pathology*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000235:genetics; D009361:Neoplasm Invasiveness; D018919:Neovascularization, Physiologic; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D052243:Resistin / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D014471:Umbilical Veins; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D012333:RNA, Messenger; D052243:Resistin; D019715:Tissue Inhibitor of Metalloproteinase-1; D042461:Vascular Endothelial Growth Factor A; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2