Preclinical Evidence of STAT3 Inhibitor Pacritinib Overcoming Temozolomide Resistance via Downregulating miR-21-Enriched Exosomes from M2 Glioblastoma-Associated Macrophages.

ABSTRACT: The tumor microenvironment (TME) plays a crucial role in virtually every aspect of tumorigenesis of glioblastoma multiforme (GBM). A dysfunctional TME promotes drug resistance, disease recurrence, and distant metastasis. Recent evidence indicates that exosomes released by stromal cells within the TME may promote oncogenic phenotypes via transferring signaling molecules such as cytokines, proteins, and microRNAs. In this study, clinical GBM samples were collected and analyzed. We found that GBM-associated macrophages (GAMs) secreted exosomes which were enriched with oncomiR-21. Coculture of GAMs (and GAM-derived exosomes) and GBM cell lines increased GBM cells' resistance against temozolomide (TMZ) by upregulating the prosurvival gene programmed cell death protein 4 (PDCD4) and stemness mar

SUBMITTER: Chuang HY 

PROVIDER: S-EPMC6678764 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature