Speaker
Description
Glioblastoma (GBM) remains a devastating malignancy with limited therapeutic options. Emerging evidence highlights the role of connexins in tumor progression. In this study, we investigate the therapeutic potential of abEC1.1, a monoclonal antibody that inhibits connexin hemichannels (HCs), addressing the need for targeted therapies for GBM.
To evaluate the effects of abEC1.1 on patient-derived GBM cell cultures (hGBM-13), two assays of HC functionality were performed at single cell level: DAPI and $Ca^{2+}$ uptake (via GCaMP6s $Ca^{2+}$ indicator). Given that ATP and glutamate are two key factors contributing to glioma invasiveness, release assays of ATP, probed by luciferin-luciferase bioluminescence, and glutamate, by iGluSnFr fluorescence, were also carried out.
Compared to untreated controls, the uptake rate of DAPI was reduced by 47% in hGBM-13 cultures treated with abEC1.1. Antibody treatment reduced by 65% the cytosolic $Ca^{2+}$ load triggered by an increase of the extracellular free [$Ca^{2+}$] from 0 mM to 2 mM. Incubation with abEC1.1 significantly limited ATP (by 18%) and glutamate (by 44%) release.
$Ca^{2+}$ signaling regulates key downstream pathways that drive proliferation, invasion, and resistance to apoptosis, while ATP supports tumor migration, and glutamate release promotes excitotoxicity. Therefore, by attenuating these signals, abEC1.1 has shown potential to directly impact the molecular mechanisms underpinning GBM aggressiveness.