Delivery of MGMT mRNA to glioma cells by reactive astrocyte-derived exosomes confers a temozolomide resistance phenotype

Yu, Tianfu, XieFeng Wang, Tongle Zhi, Junxia Zhang, Yingyi Wang, Er Nie, Fengqi Zhou, Yongping You, and Ning Liu. "Delivery of MGMT mRNA to glioma cells by reactive astrocyte-derived exosomes confers a temozolomide resistance phenotype." Cancer letters (2018).

The glioma-astrocyte interaction plays an important role in tumor microenvironment remodeling; however, the underlying mechanism has not been completely clarified. In this study, we show that glioma cells stimulate normal human astrocyte (NHA) into reactive astrocyte (RAS) in a non-contact manner. Additionally, the amount of O6-alkylguanine DNA alkyltransferase (MGMT) mRNA in exosomes (EXOs) released by RAS was significantly increased compared with that in non-reactive NHA. Importantly, MGMT-negative glioma cells can take up RAS-EXOs and acquire a temozolomide (TMZ)-resistant phenotype via the translation of exogenous exosomal MGMT mRNA both in vitro and in vivo. Our findings illuminate a novel phenomenon that may be a potent mechanism underlying glioma recurrence in which glioma-associated NHAs protect MGMT-negative glioma cells from TMZ-induced apoptosis by the functional intercellular transfer of exosomal MGMT mRNA.

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