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Deciphering and targeting the invasive nature of Diffuse Intrinsic Pontine Glioma

Description du projet

Comprendre la nature invasive des tumeurs cérébrales pédiatriques de haut grade

Le gliome infiltrant du tronc cérébral (GITC) est un cancer infantile agressif du tronc cérébral. Il s’agit d’une maladie terminale dont la survie globale médiane est de 9 mois. Le projet CANCER INVASION, financé par l’UE, vise à comprendre les mécanismes de croissance invasive du GITC. Les chercheurs utiliseront des techniques d’imagerie et de transcriptomique de pointe pour étudier des modèles murins de la maladie et acquérir des connaissances sur la progression du GITC dans le cerveau en développement. La mise en œuvre de l’imagerie 3D à grande échelle à résolution unicellulaire et de la microscopie intravitale permettra de visualiser le comportement des cellules tumorales chez des souris vivantes. Le projet fournira des connaissances fondamentales sur les mécanismes d’invasion des cellules cancéreuses qui régissent la propagation du GITC et pourrait identifier de nouvelles cibles thérapeutiques potentielles pour cette maladie mortelle.

Objectif

Introduction: The ability of a cancer cell to invade into the surrounding tissue is the main feature of malignant cancer progression. Diffuse Intrinsic Pontine Glioma (DIPG) is a paediatric high-grade brain tumour with no chance of survival due to its highly invasive nature.
Goal: By combining state-of-the-art imaging and transcriptomics, we aim to identify and target the key mechanisms driving the highly invasive growth of DIPG.
Technology advances: Two unique single cell resolution imaging techniques that we have recently developed will be implemented: Large-scale Single-cell Resolution 3D imaging (LSR-3D) that allows visualization of complete tumour specimens and intravital microscopy using a cranial imaging window that allows imaging of tumour cell behaviour in living mice. In addition, we will apply a technique of live imaging Patch-seq to perform behaviour studies together with single cell RNA profiling.
Expected results: Using a glioma murine model in which the disease is induced in neonates and a new embryonic model based on in utero electroporation, we expect to gain knowledge on the progression of DIPG in maturing brain. LSR-3D imaging on human and murine specimens will provide insight into the cellular tumour composition and its integration in the neuroglial network. With intravital imaging, we will characterize invasive cancer cell behaviour and functional connections with healthy brain cells. In combination with Patch-seq, we will identify transcriptional program(s) specific to invasive behaviour. Altogether, we expect to identify novel key players in cancer invasion and assess their potential to prevent DIPG progression. 
Future perspective: With the studies proposed, we will gain fundamental insights into the cancer cell invasion mechanisms that govern DIPG which may provide new potential therapeutic target(s) for this dismal disease. Overall, the knowledge and advanced technologies obtained here will be of great value for the tumour biology field.

Régime de financement

ERC-STG - Starting Grant

Coordinateur

PRINSES MAXIMA CENTRUM VOOR KINDERONCOLOGIE BV
Contribution nette de l'UE
€ 1 500 000,00
Adresse
Heidelberglaan 25
3584CS Utrecht
Pays-Bas

Voir sur la carte

Région
West-Nederland Utrecht Utrecht
Type d’activité
Other
Liens
Coût total
€ 1 500 000,00

Bénéficiaires (1)