Study of the CXCL12-CXCR4/ACKR3 signaling in glioblastoma and of its importance in the control of translation and relapses

Project Details

Description

Glioblastoma (GBM) is the most common primary tumor of the nervous system with a median survival of 16 months, despite the combination of radio and chemotherapy after surgical resection. This poor prognosis is the result of systematic relapses. It is clearly demonstrated that GBMs are heterogeneous in the sense that only a small population of tumor cells, the GBM initiating cells (CIG), are capable of giving rise to a tumor. Using an in vivo model (GBM xenograft in the striatum of nude mice), we demonstrated that certain GBM cells migrate specifically to the subventricular zone (ZSV), one of the two neurogenic regions of the adult brain. These GBM cells nestled in ZSV are in fact CIGs and we have shown that their level of protein synthesis is very high compared to cells of the tumor mass. This specific invasion is due to the secretion by the ZSV of CXCL12 acting via the CXCR4 receptors expressed by tumor cells. In addition, this CXCL12 induces the radio resistance of GBM cells. CXCL12 can also interact with the ACKR3 / CXCR7 receptor whose affinity for CXCL12 is ten times higher than that of CXCR4. Finally, we recently observed that CXCL12 modulates the phosphorylation of several proteins involved in the regulation of translation. In this project we propose 1) to study the expression and the role of ACKR3 in GBM; 2) to investigate how CXCL12 signaling modulates protein.
AcronymACKR3/CXCL12 axis in GBM
StatusActive
Effective start/end date3/05/2130/05/25

Funding

  • FNR - Fonds National de la Recherche: €439,000.00

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