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Deciphering and targeting the invasive nature of Diffuse Intrinsic Pontine Glioma

Descrizione del progetto

Comprendere la natura invasiva dei tumori cerebrali di alto grado in età pediatrica

Il glioma diffuso intrinseco del ponte (DIPG) è un tumore infantile aggressivo del tronco encefalico. È una malattia terminale con una sopravvivenza mediana generale di 9 mesi. Il progetto CANCER INVASION, finanziato dall’UE, si propone di comprendere i meccanismi che provocano la crescita invasiva del DIPG. I ricercatori utilizzeranno tecniche di imaging e trascrittomica d’avanguardia per studiare modelli murini della malattia e acquisire conoscenze sulla progressione del DIPG nel cervello in via di sviluppo. L’attuazione dell’imaging 3D a risoluzione monocellulare su larga scala e della microscopia intravitale consentirà l’imaging del comportamento delle cellule tumorali nei topi vivi. Il progetto fornirà conoscenze fondamentali sui meccanismi di invasione delle cellule tumorali che regolano la diffusione del DIPG e potrà identificare nuovi potenziali bersagli terapeutici per questa patologia mortale.

Obiettivo

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.

Meccanismo di finanziamento

ERC-STG - Starting Grant

Coordinatore

PRINSES MAXIMA CENTRUM VOOR KINDERONCOLOGIE BV
Contribution nette de l'UE
€ 1 500 000,00
Indirizzo
Heidelberglaan 25
3584CS Utrecht
Paesi Bassi

Mostra sulla mappa

Regione
West-Nederland Utrecht Utrecht
Tipo di attività
Other
Collegamenti
Costo totale
€ 1 500 000,00

Beneficiari (1)