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CALM-GBM: Circuit control by Astrocytes Located in Microenvironment of Glioblastoma

Descrizione del progetto

Astrociti e sinapsi nella progressione del glioblastoma

Il glioblastoma (GBM) è un tumore cerebrale aggressivo e incurabile che viene trattato attraverso l’asportazione chirurgica, seguita da radioterapia e chemioterapia. Le cellule del GBM possono formare connessioni sinaptiche con i neuroni sani, note come sinapsi del neuroglioma (SNG), che aiutano le cellule tumorali a sopravvivere e a infiltrarsi nel cervello normale. Anche gli astrociti associati al tumore hanno un ruolo nella promozione della crescita tumorale, ma il loro esatto contributo alla progressione del GBM rimane poco chiaro. Con il sostegno del programma di azioni Marie Skłodowska-Curie, il progetto CALM-GBM userà la microscopia a super-risoluzione per misurare la copertura gliale delle SNG in campioni di GBM umani e murini. Studierà inoltre la segnalazione del calcio tra le cellule di GBM e i gli astrociti associati al tumore, per capire meglio come questi ultimi favoriscano la crescita del tumore e per scoprire il ruolo delle cellule astrogliali nella progressione del GBM.

Obiettivo

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

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Invito a presentare proposte

(si apre in una nuova finestra) HORIZON-MSCA-2024-PF-01

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Coordinatore

KATHOLIEKE UNIVERSITEIT LEUVEN
Contributo netto dell'UE
€ 216 240,00
Indirizzo
OUDE MARKT 13
3000 Leuven
Belgio
Regione
Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
Nessun dato