Journal
CANCER LETTERS
Volume 433, Issue -, Pages 210-220Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2018.06.041
Keywords
Glioma; Temozolomide; Exosomes; Astrocyte; Microenvironment
Categories
Funding
- National Key Research and Development Plan [2016YFC0902500]
- National Natural Science Foundation of China [81772682, 81672501]
- Jiangsu Province's Natural Science Foundation [20170108, 20151585]
- Program for Advanced Talents within Six Industries of Jiangsu Province [2015-WSN-036, 2016-WSW-013]
- Jiangsu Province's Key Discipline of Medicine [ZDXKA2016001]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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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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