Placenta derived mesenchymal stem cells (PDMSCs) modulate HIF-1a, VEGF and JunB genes in ovarian cancer cells.

Abstract

Ovarian cancer (OC) has the highest mortality rate of all gynecological cancers. We previously demonstrated that PDMSCs produce soluble factors able to inhibit OC cell cycle and growth through a pathway that still remains to be determined. Hypoxia Inducible Factor-1 alpha (HIF-1a), main player in cellular response to hypoxia, promotes the expression of VEGF, responsible for neo-angiogenesis. HIF-1a overexpression has been described in most human malignancies and it is linked to bad cancer prognosis. Activating Protein-1 (AP-1) molecules are pivotal regulators of OC cell cycle progression and metastatization. Herein, we investigated HIF-1a, VEGF and JunB expression in OC ES-2 and SKOV-3 cells treated by PDMSCs conditioned medium (CM) in order to verify our hypothesis that PDMSCs could act through the modulation of HIF-1a and anti-proliferative AP-1 molecules.Methods: PDMSCs were isolated from physiological human term placentae (n=12). CM will be produced by incubating PDMSCs for 24-48 hours in DMEM medium. CM will be harvested and filtered to remove cellular debris. ES-2 and SKOV-3 cells were treated by 24/48h CMs for 24h or 48h and mRNA was isolated. Expression of HIF-1a, VEGF and JunB was assessed by Real Time PCR.