"CNECZ.02.1.01/0.0/0.0/16_019/0000785" Dotaz Zobrazit nápovědu
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.
- MeSH
- endopeptidasy MeSH
- extracelulární matrix * metabolismus patologie MeSH
- fibronektiny * metabolismus MeSH
- glioblastom patologie metabolismus MeSH
- gliom * patologie metabolismus MeSH
- kolagen typu I metabolismus MeSH
- lidé MeSH
- membránové proteiny metabolismus MeSH
- nádorové buněčné linie MeSH
- nádorové mikroprostředí fyziologie MeSH
- nádory mozku * patologie metabolismus MeSH
- pericyty * metabolismus patologie MeSH
- pohyb buněk fyziologie MeSH
- serinové endopeptidasy metabolismus MeSH
- želatinasy metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH