Efficacy of Combined Tumor Irradiation and K3.1-targeting with TRAM-34 in a Syngeneic Glioma Mouse Model

Overview

Journal Sci Rep

Specialty Science

Date 2023 Nov 23

PMID 37996600

Authors

Nicolai Stransky

Katrin Ganser

Leticia Quintanilla-Martinez

Irene Gonzalez-Menendez

Ulrike Naumann

Franziska Eckert

Pierre Koch

Stephan M Huber

Peter Ruth

Affiliations

Soon will be listed here.

Abstract

The intermediate-conductance calcium-activated potassium channel K3.1 has been proposed to be a new potential target for glioblastoma treatment. This study analyzed the effect of combined irradiation and K3.1-targeting with TRAM-34 in the syngeneic, immune-competent orthotopic SMA-560/VM/Dk glioma mouse model. Whereas neither irradiation nor TRAM-34 treatment alone meaningfully prolonged the survival of the animals, the combination significantly prolonged the survival of the mice. We found an irradiation-induced hyperinvasion of glioma cells into the brain, which was inhibited by concomitant TRAM-34 treatment. Interestingly, TRAM-34 did neither radiosensitize nor impair SMA-560's intrinsic migratory capacities in vitro. Exploratory findings hint at increased TGF-β1 signaling after irradiation. On top, we found a marginal upregulation of MMP9 mRNA, which was inhibited by TRAM-34. Last, infiltration of CD3, CD8 or FoxP3 T cells was not impacted by either irradiation or K3.1 targeting and we found no evidence of adverse events of the combined treatment. We conclude that concomitant irradiation and TRAM-34 treatment is efficacious in this preclinical glioma model.

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