Myeloid cells coordinately induce glioma cell-intrinsic and cell-extrinsic pathways for chemoresistance via GP130 signaling.

ABSTRACT: The DNA damage response (DDR) and the blood-tumor barrier (BTB) restrict chemotherapeutic success for primary brain tumors like glioblastomas (GBMs). Coherently, GBMs almost invariably relapse with fatal outcomes. Here, we show that the interaction of GBM and myeloid cells simultaneously induces chemoresistance on the genetic and vascular levels by activating GP130 receptor signaling, which can be addressed therapeutically. We provide data from transcriptomic and immunohistochemical screens with human brain material and pharmacological experiments with a humanized organotypic GBM model, proteomics, transcriptomics, and cell-based assays and report that nanomolar concentrations of the signaling peptide humanin promote temozolomide (TMZ) resistance through DDR activation. GBM mouse models re

SUBMITTER: Cheng J 

PROVIDER: S-EPMC11384956 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature