Glioblastomas are deadly neoplasms resistant to current treatment modalities. Fibroblast activation protein (FAP) is a protease which is not expressed in most of the normal adult tissues but is characteristically present in the stroma of extracranial malignancies. FAP is considered a potential therapeutic target and is associated with a worse patient outcome in some cancers. The FAP localization in the glioma microenvironment and its relation to patient survival are unknown. By analyzing 56 gliomas and 15 non-tumorous brain samples, we demonstrate increased FAP expression in a subgroup of high-grade gliomas, in particular on the protein level. FAP expression was most elevated in the mesenchymal subtype of glioblastoma. It was neither associated with glioblastoma patient survival in our patient cohort nor in publicly available datasets. FAP was expressed in both transformed and stromal cells; the latter were frequently localized around dysplastic blood vessels and commonly expressed mesenchymal markers. In a mouse xenotransplantation model, FAP was expressed in glioma cells in a subgroup of tumors that typically did not express the astrocytic marker GFAP. Endogenous FAP was frequently upregulated and part of the FAP+ host cells coexpressed the CXCR4 chemokine receptor. In summary, FAP is expressed by several constituents of the glioblastoma microenvironment, including stromal non-malignant mesenchymal cells recruited to and/or activated in response to glioma growth. The limited expression of FAP in healthy tissues together with its presence in both transformed and stromal cells suggests that FAP may be a candidate target for specific delivery of therapeutic agents in glioblastoma.

• Klíčová slova
• Fibroblast activation protein α, Glioma, Seprase, Serine protease, Stromal cells,
• MeSH
• apoptóza MeSH
• buňky stromatu metabolismus   patologie   MeSH
• dospělí MeSH
• endopeptidasy MeSH
• fibroblasty metabolismus   patologie   MeSH
• glioblastom genetika   metabolismus   patologie   MeSH
• imunoenzymatické techniky MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny genetika   metabolismus   MeSH
• messenger RNA genetika   MeSH
• mezoderm metabolismus   patologie   MeSH
• míra přežití MeSH
• myši inbrední NOD MeSH
• myši MeSH
• nádorové biomarkery metabolismus   MeSH
• nádorové buňky kultivované MeSH
• následné studie MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• prognóza MeSH
• proliferace buněk MeSH
• senioři MeSH
• serinové endopeptidasy genetika   metabolismus   MeSH
• staging nádorů MeSH
• studie případů a kontrol MeSH
• transformované buněčné linie metabolismus   patologie   MeSH
• western blotting MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• želatinasy genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• endopeptidasy MeSH
• fibroblast activation protein alpha MeSH Prohlížeč
• membránové proteiny MeSH
• messenger RNA MeSH
• nádorové biomarkery MeSH
• serinové endopeptidasy MeSH
• želatinasy MeSH