Projects

There is an urgent need for new biochemical tools to better decipher the role of different proteases in the invasion of the brain tumour glioblastoma to successfully target the invasive and refractory cancer stem cells. Metalloproteases (MMPs) 2 and 9 are associated with high tumor grades and tumour progression and are crucial molecules for invasion and interactions of cancer cells with the tumour microenvrionment. The goal of this project is to develop and evaluate metalloprotease MMP-2/9 selective chemical probes to map and inhibit their activity in glioblastoma tissue from patients and in advanced in vitro tumour models.

The specific objectives are:

- design and develop selective reactive probes for MMP-2 and -9 to produce both imaging agents and covalent inhibitors,

- determine the localization, expression and activity of MMP-2/9 in glioblastoma biopsies and organoids, and

- test the effect of MMP-2/9 inhibitors on glioblastoma stem cell and organoid invasion.

The novelty of this strategy is the development of selective MMP inhibitors and the ability to profile MMPs in advanced tumour models. This will lead to a better understanding of glioblastoma progression and the possibility of inhibiting MMP-2/9 in glioblastoma in vivo.

Project phases

1)    Development of new activity-based probes to target metalloproteass MMP-2 and MMP-9

Performed by CEA

2)    Definining localization and activities of MMP-2/9 in GBM tissues, organoids and cells using selective antibodies and probes

Performed by NIB

Project group: https://cris.cobiss.net/ecris/si/sl/project/19737

Bibliographic information and other information about the project SICRIS: https://cris.cobiss.net/ecris/si/sl/project/19737