Laminin-associated integrins mediate Diffuse Intrinsic Pontine Glioma infiltration and therapy response within a neural assembloid model.
Acta Neuropathol Commun
; 12(1): 71, 2024 05 05.
Article
en En
| MEDLINE
| ID: mdl-38706008
ABSTRACT
Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive and fatal pediatric brain cancer. One pre-requisite for tumor cells to infiltrate is adhesion to extracellular matrix (ECM) components. However, it remains largely unknown which ECM proteins are critical in enabling DIPG adhesion and migration and which integrin receptors mediate these processes. Here, we identify laminin as a key ECM protein that supports robust DIPG cell adhesion and migration. To study DIPG infiltration, we developed a DIPG-neural assembloid model, which is composed of a DIPG spheroid fused to a human induced pluripotent stem cell-derived neural organoid. Using this assembloid model, we demonstrate that knockdown of laminin-associated integrins significantly impedes DIPG infiltration. Moreover, laminin-associated integrin knockdown improves DIPG response to radiation and HDAC inhibitor treatment within the DIPG-neural assembloids. These findings reveal the critical role of laminin-associated integrins in mediating DIPG progression and drug response. The results also provide evidence that disrupting integrin receptors may offer a novel therapeutic strategy to enhance DIPG treatment outcomes. Finally, these results establish DIPG-neural assembloid models as a powerful tool to study DIPG disease progression and enable drug discovery.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Integrinas
/
Laminina
/
Neoplasias del Tronco Encefálico
/
Glioma Pontino Intrínseco Difuso
Límite:
Humans
Idioma:
En
Revista:
Acta Neuropathol Commun
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos