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

Cheng J, Li M, Motta E, Barci D, Song W, Zhou D, Li G, Zhu S, Yang A, Vaillant BD, Imhof A, Forné I and 7 more

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Spiegl-Kreinecker S, Zhang N, Katayama H, Bhat KPL, Flüh C, Kälin RE, Glass R

Cell reports. Medicine24 Jul 2024Cited by 8 (Europe PMC)

PMID39053460PMCIDPMC11384956DOI10.1016/j.xcrm.2024.101658PepBankPUB-39053460

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Summary

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 recapitulating intratumoral humanin release show accelerated BTB formation. GP130 blockade attenuates both DDR activity and BTB formation, resulting in improved preclinical chemotherapeutic efficacy. Altogether, we describe an overarching mechanism for TMZ resistance and outline a translatable strategy with predictive markers to improve chemotherapy for GBMs.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

1 result from studies that gave the peptide. No result from this study comes from people.

01LabIn vitro (cells)Mechanism
In glioblastoma models and cell assays, nanomolar concentrations of humanin promoted temozolomide resistance through DDR activation.
In plain wordsIn lab models of glioblastoma, small amounts of humanin made tumor cells more resistant to temozolomide by switching on DNA damage repair.
Peptide
Humanin
Outcome
IncreaseTemozolomide resistance via DDR activation
Study
n: not reported in source
Humanized organotypic GBM model and cell-based assays
Outcome group
Tumor growth · Cancer
Studied dose
nanomolar concentrationsAs given in this study.
Source sentences
Summary
report that nanomolar concentrations of the signaling peptide humanin promote temozolomide (TMZ) resistance through DDR activation.
Show in the study text Report a problemFND-3905346001

Studies that did not test the peptide alone2

In this study, Humanin was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Humanin.

02AnimalNot a test of Humanin aloneAnimal study (in vivo)Mechanism
In GBM mouse models that recapitulate intratumoral humanin release, blood-tumor barrier formation was accelerated.
In plain wordsIn mice that model humanin release inside glioblastoma, the blood-tumor barrier formed faster.
Peptide
Humanin
Outcome
IncreaseBlood-tumor barrier formation with intratumoral humanin release
Study
mousen: not reported in source
GBM mouse models recapitulating intratumoral humanin release
Outcome group
Tumor growth · Cancer
Source sentences
Summary
GBM mouse models recapitulating intratumoral humanin release show accelerated BTB formation.
In this study, Humanin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Humanin.
Show in the study text Report a problemFND-3905346002
03AnimalNot a test of Humanin aloneAnimal study (in vivo)Efficacy outcome
In preclinical glioblastoma models, GP130 blockade attenuated DDR activity and blood-tumor barrier formation and improved chemotherapeutic efficacy.
In plain wordsIn preclinical glioblastoma models, blocking GP130 weakened DNA repair and barrier formation, and chemotherapy worked better.
Peptide
Humanin
Outcome
DecreaseGP130 blockade effect on DDR activity, BTB formation and chemotherapy efficacy
Study
n: not reported in source
Preclinical GBM models
Outcome group
Tumor growth · Cancer
Source sentences
Summary
GP130 blockade attenuates both DDR activity and BTB formation, resulting in improved preclinical chemotherapeutic efficacy.
In this study, Humanin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Humanin.
Show in the study text Report a problemFND-3905346003

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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