AIRC IG 2021 (DFM.AD004.319)

Area tematica

Scienze fisiche e tecnologie della materia

Area progettuale

Struttura responsabile del progetto di ricerca

Istituto di Nanotecnologia (NANOTEC)

Responsabile di progetto

BARBARA CORTESE
Telefono: 3291171375
E-mail: barbara.cortese@cnr.it

Abstract

Invasiveness is a key hallmark of glioblastoma (GBM) which renders complete surgical resection impossible. Increasing work unequivocally shows biophysical cues in the microenvironment drives their progression. So far, the key mechanisms and impact of interstitial fluid flow (IFF)/hypoxia/electric-cues associated to biomechanical force on intrinsic tumour cell biology and malignancy remains poorly understood. Development of effective treatments for GBM requires 3D experimental models that mimic more closely the tumour microenvironment and thus, can provide clinically translatable results. Experimentally, the Hippo pathway and signalling transcription factors, YAP/TAZ, are central for cell migration proliferation and angiogenesis. How these pathways in a 3D and mechanically variable environment as well as under influence of other conditions such as electric fields, IFF and hypoxia are yet to be defined. Which are the overriding effects and how these cues may affect other primary cell functions directly related to metastasis, including proliferation and evasion of apoptosis will be explored.

Obiettivi

Engineering a 3D tumour model with a tunable mechanotactic environment will allow for spatial mapping of cellular outcomes in response to these key factors characterizing GBM. Goals involve recreation of a 3D brainlike environment with mechanotactic cues to uncover key tumour cell properties significant to invasion. We also aim to investigate both the integrated and decoupled effects of each feature (hypoxia, IFF, electric fields) to identify molecular pathways and the role for YAP/TAZ activation in the progression and response of GSCs.Bioengineered scaffolds enabling modular control over these independent variables can potentially isolate these effects and identify new therapeutic targets. We propose to address 1) how variation of 3D mechanical stiffness influences GSC cells; 2) investigate the Hippo pathway related to the ECM in 3D environments; and 3) study cell response to individual and concurrent key factors of the GBM such as hypoxia and interstitial fluid flow and electric fields.

Data inizio attività

02/01/2022

Parole chiave

Glioma and/or glioblastoma, Cell migration, Biophysics;

Ultimo aggiornamento: 13/12/2024