Circuitcontrole door astrocyten in de micro-omgeving van glioblastoom (CALM-GBM)

Glioblastoma (GBM) is an incurable brain tumor, with current treatments primarily focused on surgical removal. Although the tumor core is often successfully excised, invasive GBM cells that extend beyond the surgical margins persist, leading to recurrence. To improve patient outcomes, it is crucial to advance research that targets these invasive cells and elucidates the mechanisms enabling their survival within healthy brain tissue.

Recent studies have revealed that the invasive cells of GBM, which contribute to the tumor’s resilience against treatment, can establish synaptic connections with nearby healthy neurons. These connections, termed neuroglioma synapses (NGS), facilitate an electrical coupling that activates GBM cells and supports their survival. In the healthy brain, 90% of synaptic connections are encapsulated by astrocytes, forming what is known as a tripartite synapse. However, it remains unclear whether NGS between GBM cells and neurons are similarly ensheathed by astrocytes.

The astrocytes surrounding the tumor, known as Tumor-Associated Astrocytes (TAAs), enter a reactive state in the presence of GBM, where they are implicated in promoting tumor growth. Emerging evidence suggests that TAAs are functionally connected to GBM cells through gap junctions, enabling the transfer of calcium signals. Despite this, the role of TAAs in facilitating GBM progression via a functional calcium network remains poorly understood.

The objectives of this proposal are:

1. Quantify by super resolution microscopy the glial coverage of NGS in human GBM samples and in mouse model
2. Measure the calcium dynamics between the GBM and TAAs to understand better the functional network that makes TAAs promote tumor growth.

This research will pioneer new directions in cancer neuroscience by identifying the role of astroglial cells in GBM progression and potentially guiding the development of targeted therapeutic strategies aimed at disrupting these supportive networks. t