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Fibroblast activation protein alpha is expressed by transformed and stromal cells and is associated with mesenchymal features in glioblastoma

Busek, Petr
Author Busek, Petr Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53, Prague 2, Czech Republic. busekpetr@seznam.cz
Balaziova, Eva
Author Balaziova, Eva Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53, Prague 2, Czech Republic
Matrasova, Ivana
Author Matrasova, Ivana Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53, Prague 2, Czech Republic
Hilser, Marek
Author Hilser, Marek Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53, Prague 2, Czech Republic
Tomas, Robert
Author Tomas, Robert Department of Neurosurgery, Na Homolce Hospital, Roentgenova 2, 150 30, Prague 5, Czech Republic
Syrucek, Martin
Author Syrucek, Martin Department of Pathology, Na Homolce Hospital, Roentgenova 2, 150 30, Prague 5, Czech Republic
Zemanova, Zuzana
Author Zemanova, Zuzana Institute of Clinical Biochemistry and Laboratory Diagnostics of the First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, U Nemocnice 2, 128 01, Prague 2, Czech Republic
Krepela, Evzen
Author Krepela, Evzen Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53, Prague 2, Czech Republic
Belacek, Jaromir
Author Belacek, Jaromir Institute of Biophysics and Bioinformatics, First Faculty of Medicine, Charles University in Prague, Salmovská 1, 120 00, Prague 2, Czech Republic
Sedo, Aleksi
Author Sedo, Aleksi Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53, Prague 2, Czech Republic. aleksi@cesnet.cz

Tumour biology. 2016 Oct ; 37 (10) : 13961-13971. [epub] 20160804

Tumour Biol
ISSN 1423-0380 | 1010-4283
Source

Language English Country United States Media print-electronic

Document type Comparative Study, Journal Article

Persistent link https://www.medvik.cz/link/pmid27492457

PubMed 27492457
DOI 10.1007/s13277-016-5274-9
PII: 10.1007/s13277-016-5274-9
Knihovny.cz E-resources

Keywords
Fibroblast activation protein α, Glioma, Seprase, Serine protease, Stromal cells,
MeSH
Apoptosis MeSH
Stromal Cells metabolism pathology MeSH
Adult MeSH
Endopeptidases MeSH
Fibroblasts metabolism pathology MeSH
Glioblastoma genetics metabolism pathology MeSH
Immunoenzyme Techniques MeSH
Real-Time Polymerase Chain Reaction MeSH
Middle Aged MeSH
Humans MeSH
Membrane Proteins genetics metabolism MeSH
RNA, Messenger genetics MeSH
Mesoderm metabolism pathology MeSH
Survival Rate MeSH
Mice, Inbred NOD MeSH
Mice MeSH
Biomarkers, Tumor metabolism MeSH
Tumor Cells, Cultured MeSH
Follow-Up Studies MeSH
Reverse Transcriptase Polymerase Chain Reaction MeSH
Prognosis MeSH
Cell Proliferation MeSH
Aged MeSH
Serine Endopeptidases genetics metabolism MeSH
Neoplasm Staging MeSH
Case-Control Studies MeSH
Cell Line, Transformed metabolism pathology MeSH
Blotting, Western MeSH
Xenograft Model Antitumor Assays MeSH
Gelatinases genetics metabolism MeSH
Animals MeSH
Check Tag
Adult MeSH
Middle Aged MeSH
Humans MeSH
Male MeSH
Mice MeSH
Aged MeSH
Female MeSH
Animals MeSH
Publication type
Journal Article MeSH
Comparative Study MeSH
Names of Substances
Endopeptidases MeSH
fibroblast activation protein alpha MeSH Browser
Membrane Proteins MeSH
RNA, Messenger MeSH
Biomarkers, Tumor MeSH
Serine Endopeptidases MeSH
Gelatinases MeSH

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.

Department of Neurosurgery Na Homolce Hospital Roentgenova 2 150 30 Prague 5 Czech Republic

Department of Pathology Na Homolce Hospital Roentgenova 2 150 30 Prague 5 Czech Republic

Institute of Biochemistry and Experimental Oncology 1st Faculty of Medicine Charles University Prague U Nemocnice 5 128 53 Prague 2 Czech Republic

Institute of Biophysics and Bioinformatics 1st Faculty of Medicine Charles University Prague Salmovská 1 120 00 Prague 2 Czech Republic

Institute of Clinical Biochemistry and Laboratory Diagnostics of the 1st Faculty of Medicine Charles University Prague and General University Hospital Prague U Nemocnice 2 128 01 Prague 2 Czech Republic

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