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
• Endopeptidases MeSH
• Extracellular Matrix * metabolism   pathology   MeSH
• Fibronectins * metabolism   MeSH
• Glioblastoma pathology   metabolism   MeSH
• Glioma * pathology   metabolism   MeSH
• Collagen Type I metabolism   MeSH
• Humans MeSH
• Membrane Proteins metabolism   MeSH
• Cell Line, Tumor MeSH
• Tumor Microenvironment physiology   MeSH
• Brain Neoplasms * pathology   metabolism   MeSH
• Pericytes * metabolism   pathology   MeSH
• Cell Movement physiology   MeSH
• Serine Endopeptidases metabolism   MeSH
• Gelatinases metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH