Work

Collagen VI deposition primes the glioblastoma microenvironment for invasion through mechanostimulation of β-catenin signaling

Year: 2024

Type: article

Abstract: While glioblastoma (GBM) progression is associated with extensive extracellular matrix (ECM) secretion, the causal contributions of ECM secretion to invasion remain unclear. Here we investigate these contributions by combining engineered materials, proteomics, analysis of patient data, and a model of bevacizumab-resistant GBM. We find that GBM cells cultured in engineered 3D hyaluronic acid hydrogels secrete ECM prior to invasion, particularly in the absence of exogenous ECM ligands. Proteomic measurements reveal extensive secretion of collagen VI, and collagen VI-associated transcripts are correspondingly enriched in microvascular proliferation regions of human GBMs. We further show that bevacizumab-resistant GBM cells deposit more collagen VI than their responsive counterparts, which is associated with marked cell-ECM stiffening. COL6A3 deletion in GBM cells reduces invasion, β-catenin signaling, and expression of mesenchymal markers, and these effects are amplified in hypoxia. Our studies strongly implicate GBM cell-derived collagen VI in microenvironmental remodeling to facilitate invasion.

Source: PNAS Nexus

DOI: 10.1093/pnasnexus/pgae355

Authors: Junghwa Cha, Erika A Ding, Emily M Carvalho, Annabelle Fowler, Manish K Aghi, Sanjay Kumar

Institutions: University of California, Berkeley, University of California, San Francisco

Language: English

Topic: Glioma Diagnosis and Treatment

Subfield: Genetics (clinical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,202