Role of regulatory and angiogenic cytokines in invasion of trophoblastic cells.
OBJECTIVE
Trophoblast invasion is a temporally and locally restricted process, which regulates implantation and oxygen arrival to the embryo through the dialog with spiral artery endothelium. Trophoblast factors with angiogenic potential are activated by hypoxia. Their capacities to induce proliferation, migration, and invasion of trophoblastic cells have been investigated.


METHODS
The expression of interleukin (IL)-6, CD126, CD130, vascular endothelial growth factor (VEGF), and hypoxia inducible factor-1alpha (HIF-1alpha) has been silenced in JEG-3 choriocarcinoma cells by using siRNA. Silencing efficacy has been assessed by ELISA, PCR or Western blotting. Proliferation has been measured by flow cytometry, migration by a transwell assay, and invasion by a Matrigel assay.


RESULTS
Proliferation was significantly reduced by silencing of CD126 or CD130, migration by silencing of IL-6, VEGF, or HIF-1alpha, and invasion by silencing of IL-6 and HIF-1alpha.


CONCLUSIONS
The expression of IL-6, VEGF, and HIF-1alpha in trophoblastic cells is involved in the control of trophoblast invasion and migration.
Dubinsky
Valeria
V
Reproductive Immunology, IDEHU (CONICET) - FFyB, University of Buenos Aires, Buenos Aires, Argentina.
Poehlmann
Tobias G
TG
Suman
Pankaj
P
Gentile
Teresa
T
Markert
Udo R
UR
Gutierrez
Gabriela
G
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000276:immunology*; D010064:Embryo Implantation / Q000235:genetics / Q000276:immunology*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000276:immunology*; D014327:Trophoblasts / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C508603:IL6R protein, human; D015850:Interleukin-6; D034741:RNA, Small Interfering; D019947:Receptors, Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D050822:Cytokine Receptor gp130