Regulation of Fibroblast Activation Protein by Transforming Growth Factor Beta-1 in Glioblastoma Microenvironment

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61383082%3A_____%2F21%3A00001662" target="_blank" >RIV/61383082:_____/21:00001662 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/21:10427302

Result on the web

<a href="https://pubmed.ncbi.nlm.nih.gov/33494271/" target="_blank" >https://pubmed.ncbi.nlm.nih.gov/33494271/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms22031046" target="_blank" >10.3390/ijms22031046</a>

Result language

angličtina

Original language name

Regulation of Fibroblast Activation Protein by Transforming Growth Factor Beta-1 in Glioblastoma Microenvironment

Original language description

The proline-specific serine protease fibroblast activation protein (FAP) can participate in the progression of malignant tumors and represents a potential diagnostic and therapeutic target. Recently, we demonstrated an increased expression of FAP in glioblastomas, particularly those of the mesenchymal subtype. Factors controlling FAP expression in glioblastomas are unknown, but evidence suggests that transforming growth factor beta (TGFbeta) can trigger mesenchymal changes in these tumors. Here, we investigated whether TGFbeta promotes FAP expression in transformed and stromal cells constituting the glioblastoma microenvironment. We found that both FAP and TGFbeta-1 are upregulated in glioblastomas and display a significant positive correlation. We detected TGFbeta-1 immunopositivity broadly in glioblastoma tissues, including tumor parenchyma regions in the immediate vicinity of FAP-immunopositive perivascular stromal cells. Wedemonstrate for the first time that TGFbeta-1 induces expression of FAP in non-stem glioma cells, pericytes, and glioblastoma-derived endothelial and FAP+ mesenchymal cells, but not in glioma stem-like cells. In glioma cells, this effect is mediated by the TGFbeta type I receptor and canonical Smad signaling and involves activation of FAP gene transcription. We further present evidence of FAP regulation by TGFbeta-1 secreted by glioma cells. Our results provide insight into the previously unrecognized regulation of FAP expression by autocrine and paracrine TGFbeta-1 signaling in a broad spectrum of cell types present in the glioblastoma microenvironment.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30107 - Medicinal chemistry

Project

<a href="/en/project/NV15-31379A" target="_blank" >NV15-31379A: Novel concepts for the therapeutic targeting of tumor microenvironment in human glioblastomas</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

International Journal of Molecular Sciences

ISSN

1661-6596

e-ISSN

—

Volume of the periodical

22

Issue of the periodical within the volume

3

Country of publishing house

CH - SWITZERLAND

Number of pages

20

Pages from-to

1-20

UT code for WoS article

000615286300001

EID of the result in the Scopus database

2-s2.0-85099645076