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

Content Provider	Springer Nature Link
Author	Busek, Petr Balaziova, Eva Matrasova, Ivana Hilser, Marek Tomas, Robert Syrucek, Martin Zemanova, Zuzana Krepela, Evzen Belacek, Jaromir Sedo, Aleksi
Copyright Year	2016
Abstract	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.
Starting Page	13961
Ending Page	13971
Page Count	11
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	37
Issue Number	10
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-08-04
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Fibroblast activation protein α Seprase Glioma Serine protease Stromal cells Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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