Effects of ovarian cancer secreted exosomes on cells

Ovarian cancer is the 5th most deadly cancer among women in the US and the most lethal gynecological malignancy in the world. Tumor cells release cell-secreted vesicles called exosomes. Exosomes are endosome-derived vesicles containing bioactive materials, including miRNAs that are released into the bloodstream. Importantly, stem cell factor LIN28 inhibits let-7 miRNA maturation and is present in cancer cells. We hypothesized that epithelial ovarian cancer secreted exosomes are taken up by target cells and induce a molecular and phenotypic change in cells. Our objectives were to: 1) Determine the effects of IGROV-1 cell secreted exosomes on HEK293 cells, 2) Identify genes related to the epithelial-mesenchymal transition (EMT) pathway that are modulated in HEK293 cells following exposure to IGROV-1 secreted exosomes, 3) Identify miRNAs present in IGROV-1 secreted exosomes predicted to target genes involved in EMT. Our data revealed that IGROV-1 secreted exosomes are taken up by HEK293 cells. Moreover, LIN28 is present in IGROV-1 secreted exosomes. IGROV-1 cells are more proliferative and grow in a growth inhibition manner in vitro when compared to HEK293 cells. Surprisingly, IGROV-1 secreted exosomes taken up by HEK293 cells did not affect proliferation and/or growth inhibition. However, HEK293 cells treated with IGROV-1 secreted exosomes contain increased levels of LIN28 and increased levels of various genes involved in invasion and proliferation. Elucidating the molecular and phenotypic effects ovarian cancer secreted exosomes have on cells can lead to greater understanding and insight on metastatic disease.