Yumurtalık tümör mikroçevresindeki hücrelerde tümör oluşumu ve gelişiminin eksozom aracılığıyla uyarılması

Ovarian cancer, seventh most extensive reason of cancer demise in women, has a low incidence of 3% among gynecological diseases. It is substantial to explain the carcinogenesis mechanism of ovarian cancer because of difficulties in diagnosis at early phase, prognosis at late stages, and low survival rate after surgery and chemotherapy. The purpose of this research is to demonstrate the induction of tumorigenesis in tumor microenvironment cells after uptake of oncogenic signal carrying ovarian cancer-related exosomes. Exosomes were isolated from cisplatin-resistant A2780 cells by ultrafiltration and differential centrifugation. Primary ovarian cancer (A2780), ovarian surface epithelial (OSE) and mesothelial (MeT-5A) cells were used as recipients. Isolated exosomes were characterized by western blotting and particle size analysis. Internalization of PKH26-labeled exosomes into the recipient cells was examined by confocal microscopy. Uptake mechanisms of exosomes were detected by using inhibitors via flow cytometry. The effects on the differentiation of EMT, ROS production, invasion, migration and proliferation rates were examined following exosome uptake. Isolated exosomes ranging from 30-150 nm in diameter, contained exosome marker proteins Alix and Tsg101, except ER marker; calnexin. PKH26 labeled-exosomes were internalized by recipient cells in 6 hours by different endocytic mechanisms. ROS production, invasion and migration rates increased in A2780 and OSE cells except in MeT-5A cells. EMT and proliferation were induced following exosome uptake. In conclusion, the carcinogenesis mechanism of recipient cells in the primary and secondary tumor microenvironment of ovarian cancer was induced after the uptake of ovarian cancer-released exosomes.