Background
High-grade gliomas (HGGs) are the primary cause of central nervous system cancer-related death in both children and adults. The most lethal of these cancers is glioblastoma in adults and diffuse intrinsic pontine glioma in children. Despite advances in treatments, the heterogeneous nature of HGG limits the efficacy of conventional therapies. Recent studies have revealed that neurons and HGG cells communicate using chemical and electrical signals via structures called “neurogliomal” synapses, which lead to tumour progression through neurotransmitter release from neurons onto HGG cells. Voltage-gated calcium channels (VGCCs) and their auxiliary subunits are involved in neuronal synaptic communication and have been found to play a role in other cancers by affecting the calcium signalling pathways that facilitate cell proliferation and survival. We therefore analysed the expression levels of VGCCs and their auxiliary subunits in our patient-derived cell lines and tumour samples to investigate their potential role in the progression in HGG.
Aim
The aim of this study was to identify the expression VGCCs and their auxiliary subunits in patient-derived HGG cell lines and tumour samples.
Methods
RT-qPCR was used to identify the mRNA expression of VGCCs and their auxiliary subunits in patient-derived cell lines. Western blotting and immunohistochemical techniques were used to assess their protein expression in patient-derived cell lines and tumour samples.
Results
Transcripts of the ɣ subunits of VGCCs were highly expressed at the mRNA level in patient-derived cell lines, confirmed by protein analysis in both patient-derived cell lines and tumours.
Significance and Clinical Relevance
HGG remains almost universally incurable with less than 5% of patients surviving longer than five years post diagnosis. Disrupting neurogliomal synapse function will prevent neurons delivering growth signals to HGG cells, reducing their tumorigenicity and priming them to attack by other therapies. VGCC ɣ subunits could be a potential target for this purpose