Exosomes impact survival to radiation exposure in cell line models of nervous system cancer.

Exosomes impact survival to radiation exposure in cell line models of nervous system cancer. Oncotarget. 2018 Nov 16;9(90):36083-36101 Authors: Mrowczynski OD, Madhankumar AB, Sundstrom JM, Zhao Y, Kawasawa YI, Slagle-Webb B, Mau C, Payne RA, Rizk EB, Zacharia BE, Connor JR Abstract Radiation is utilized in the therapy of more than 50% of cancer patients. Unfortunately, many malignancies become resistant to radiation over time. We investigated the hypothesis that one method of a cancer cell's ability to survive radiation occurs through cellular communication via exosomes. Exosomes are cell-derived vesicles containing DNA, RNA, and protein. Three properties were analyzed: 1) exosome function, 2) exosome profile and 3) exosome uptake/blockade. To analyze exosome function, we show radiation-derived exosomes increased proliferation and enabled recipient cancer cells to survive radiation in vitro. Furthermore, radiation-derived exosomes increased tumor burden and decreased survival in an in vivo model. To address the mechanism underlying the alterations by exosomes in recipient cells, we obtained a profile of radiation-derived exosomes that showed expression changes favoring a resistant/proliferative profile. Radiation-derived exosomes contain elevated oncogenic miR-889, oncogenic mRNAs, and proteins of the proteasome pathway, Notch, Jak-STAT, and cell cycle pathways. Radiation-derived exosomes contain decreased levels of tumor-suppressiv...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research