0601846 - ÚŽFG 2025 RIV GB eng J - Journal Article
Výmola, P. - Garcia-Borja, E. - Červenka, Jakub - Balážiová, E. - Vymolová, B. - Vepřková, J. - Vodička, Petr - Skalníková, Helena - Tomáš, R. - Netuka, D. - Bušek, P. - Šedo, A.
Fibrillar extracellular matrix produced by pericyte-like cells facilitates glioma cell dissemination.
Brain Pathology. Roč. 34, č. 6 (2024), č. článku 13265. ISSN 1015-6305. E-ISSN 1750-3639
R&D Projects: GA MŠMT LX22NPO5102; GA MŠMT(CZ) LM2023053; GA MŠMT(CZ) EF16_019/0000785
Institutional support: RVO:67985904
Keywords : collagen type I * extracellular matrix proteins * fibronectin * glioblastoma * pericytes * proteomics
OECD category: Biochemistry and molecular biology
Impact factor: 5.8, year: 2023 ; AIS: 1.854, rok: 2023
Method of publishing: Open access
Result website:
https://onlinelibrary.wiley.com/doi/10.1111/bpa.13265DOI: https://doi.org/10.1111/bpa.13265

Gliomagenesis induces profound changes in the composition of the extracellular matrix (ECM) of the brain. In this study, we identified a cellular population responsible for the increased deposition of collagen I and fibronectin in glioblastoma. Elevated levels of the fibrillar proteins collagen I and fibronectin were associated with the expression of fibroblast activation protein (FAP), which is predominantly found in pericyte-like cells in glioblastoma. FAP+ pericyte-like cells were present in regions rich in collagen I and fibronectin in biopsy material and produced substantially more collagen I and fibronectin in vitro compared to other cell types found in the GBM microenvironment. Using mass spectrometry, we demonstrated that 3D matrices produced by FAP+ pericyte-like cells are rich in collagen I and fibronectin and contain several basement membrane proteins. This expression pattern differed markedly from glioma cells. Finally, we have shown that ECM produced by FAP+ pericyte-like cells enhances the migration of glioma cells including glioma stem-like cells, promotes their adhesion, and activates focal adhesion kinase (FAK) signaling. Taken together, our findings establish FAP+ pericyte-like cells as crucial producers of a complex ECM rich in collagen I and fibronectin, facilitating the dissemination of glioma cells through FAK activation.
Permanent Link: https://hdl.handle.net/11104/0359093