Next Article in Journal
Hedgehog Signaling: Implications in Cancers and Viral Infections
Next Article in Special Issue
iPSC-Derived Hereditary Breast Cancer Model Reveals the BRCA1-Deleted Tumor Niche as a New Culprit in Disease Progression
Previous Article in Journal
Corticotropin-Releasing Hormone Receptor Alters the Tumor Development and Growth in Apcmin/+ Mice and in a Chemically-Induced Model of Colon Cancer
Article

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

1
Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, 128 53 Prague 2, Czech Republic
2
Department of Pathology, Military University Hospital Prague, 169 02 Prague 6, Czech Republic
*
Authors to whom correspondence should be addressed.
Academic Editor: Michal Masarik
Int. J. Mol. Sci. 2021, 22(3), 1046; https://doi.org/10.3390/ijms22031046
Received: 1 December 2020 / Revised: 12 January 2021 / Accepted: 18 January 2021 / Published: 21 January 2021
(This article belongs to the Special Issue Advances in Cancer Metabolism and Tumour Microenvironment)
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. View Full-Text
Keywords: glioblastoma; tumor microenvironment; transforming growth factor beta; fibroblast activation protein; seprase; regulation of expression; Smad2; signaling glioblastoma; tumor microenvironment; transforming growth factor beta; fibroblast activation protein; seprase; regulation of expression; Smad2; signaling
Show Figures

Graphical abstract

MDPI and ACS Style

Krepela, E.; Vanickova, Z.; Hrabal, P.; Zubal, M.; Chmielova, B.; Balaziova, E.; Vymola, P.; Matrasova, I.; Busek, P.; Sedo, A. Regulation of Fibroblast Activation Protein by Transforming Growth Factor Beta-1 in Glioblastoma Microenvironment. Int. J. Mol. Sci. 2021, 22, 1046. https://doi.org/10.3390/ijms22031046

AMA Style

Krepela E, Vanickova Z, Hrabal P, Zubal M, Chmielova B, Balaziova E, Vymola P, Matrasova I, Busek P, Sedo A. Regulation of Fibroblast Activation Protein by Transforming Growth Factor Beta-1 in Glioblastoma Microenvironment. International Journal of Molecular Sciences. 2021; 22(3):1046. https://doi.org/10.3390/ijms22031046

Chicago/Turabian Style

Krepela, Evzen, Zdislava Vanickova, Petr Hrabal, Michal Zubal, Barbora Chmielova, Eva Balaziova, Petr Vymola, Ivana Matrasova, Petr Busek, and Aleksi Sedo. 2021. "Regulation of Fibroblast Activation Protein by Transforming Growth Factor Beta-1 in Glioblastoma Microenvironment" International Journal of Molecular Sciences 22, no. 3: 1046. https://doi.org/10.3390/ijms22031046

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop