effects of ovarian cancer cell-derived extracellular vesicles on the proliferation and expression levels of gdf-9, amh, igf1r and foxl2 in mouse granulosa cells

Objective: granulosa cell tumor (gct) is a sex cord-stromal rare malignancy; and is associated with infertility. extracellular vesicles (evs) are small secreted vesicles containing proteins, mrna, and mirna, therefore modulating signaling pathways potentially in recipient cells and in this way, they can help cancer spread through intercellular communication. in this research, the capability of ovarian cancer-derived evs for inducing proliferation and metastasis in gcs is investigated.materials and methods: in the experimental study, evs were isolated by ultracentrifugation from a2780 human ovarian cancer cell-conditioned. mouse gcs were mechanically isolated from 8 female mice. ovarian cancer-derived evs were then added to the gcs (experimental groups: untreated gcs (control group), gcs treated with concentrations of 10, 25, and 50 μg/ml), and cell viability, migration, apoptosis, and estrogen hormone measurements were assessed by mtt, scratch assay, propidium iodide (pi) staining, annexin-v-fitc/pi and elisa assay respectively. gene’s expression of amh, foxl2, gdf-9, and igf-1r were determined using real-time polymerase chain reaction (pcr).results: gcs treated with ovarian cancer evs indicate an increase in cell viability compared to the control cells (p<0.05). also, ovarian cancer evs showed an increase in the migration potency. the other results this experimental study showed that ovarian cancer evs increase in the estrogen secretion level (p<0.001) and reduce the apoptosis of gcs compared to the control group. it is further showed that evs isolated from ovarian cancer (a2780 cell line) can induce the rna expression level of several genes in recipient gcs, such as amh, foxl2, and igf-1r (p<0.01, p<0.001), respectively, while the rna expression level of gdf-9 gene was decreased in comparison with the control.conclusion: to sum up, the research here provides a novel insight into the role of ovarian cancer evs in proliferation and metastasis in gcs and prevention of infertility caused by granulosa cancer.