Header

UZH-Logo

Maintenance Infos

TGF-β induces oncofetal fibronectin, which in turn modulates TGF-β superfamily signaling in endothelial cells


Ventura, Elisa; Weller, Michael; Macnair, Will; Eschbach, Katja; Beisel, Christian; Cordazzo, Cinzia; Claassen, Manfred; Zardi, Luciano; Burghardt, Isabel (2018). TGF-β induces oncofetal fibronectin, which in turn modulates TGF-β superfamily signaling in endothelial cells. Journal of Cell Science, 131(1):jcs.209619.

Abstract

Gene splicing profiles are frequently altered in cancer, and the splice variants of fibronectin (FN) that contain the extra-domains A (EDA) or B (EDB), referred to as EDA+FN or EDB+FN, are highly upregulated in tumor vasculature. Transforming growth factor β (TGF-β) signaling has been attributed a pivotal role in glioblastoma, with TGF-β promoting angiogenesis and vessel remodeling. By using immunohistochemistry staining, we observed that the oncofetal FN isoforms EDA+FN and EDB+FN are expressed in glioblastoma vasculature. single-cell gene expression profiling of tumors by using CD31 and α-smooth muscle actin (αSMA) as markers for endothelial cells, and pericytes and vascular smooth muscle cells (VSMCs), respectively, confirmed the predominant expression of FN, EDA+FN and EDB+FN in the vascular compartment of glioblastoma. Specifically, within the CD31-positive cell population, we identified a positive correlation between the expression of EDA+FN and EDB+FN, and of molecules associated with TGF-β signaling. Further, TGF-β induced EDA+FN and EDB+FN in human cerebral microvascular endothelial cells and glioblastoma-derived endothelial cells in a SMAD3- and SMAD4-dependent manner. In turn, we found that FN modulated TGF-β superfamily signaling in endothelial cells via the EDA and EDB, pointing towards a bidirectional influence of oncofetal FN and TGF-β superfamily signaling.

Abstract

Gene splicing profiles are frequently altered in cancer, and the splice variants of fibronectin (FN) that contain the extra-domains A (EDA) or B (EDB), referred to as EDA+FN or EDB+FN, are highly upregulated in tumor vasculature. Transforming growth factor β (TGF-β) signaling has been attributed a pivotal role in glioblastoma, with TGF-β promoting angiogenesis and vessel remodeling. By using immunohistochemistry staining, we observed that the oncofetal FN isoforms EDA+FN and EDB+FN are expressed in glioblastoma vasculature. single-cell gene expression profiling of tumors by using CD31 and α-smooth muscle actin (αSMA) as markers for endothelial cells, and pericytes and vascular smooth muscle cells (VSMCs), respectively, confirmed the predominant expression of FN, EDA+FN and EDB+FN in the vascular compartment of glioblastoma. Specifically, within the CD31-positive cell population, we identified a positive correlation between the expression of EDA+FN and EDB+FN, and of molecules associated with TGF-β signaling. Further, TGF-β induced EDA+FN and EDB+FN in human cerebral microvascular endothelial cells and glioblastoma-derived endothelial cells in a SMAD3- and SMAD4-dependent manner. In turn, we found that FN modulated TGF-β superfamily signaling in endothelial cells via the EDA and EDB, pointing towards a bidirectional influence of oncofetal FN and TGF-β superfamily signaling.

Statistics

Citations

Dimensions.ai Metrics
11 citations in Web of Science®
8 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

82 downloads since deposited on 29 Nov 2017
62 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Cell Biology
Language:English
Date:2018
Deposited On:29 Nov 2017 11:19
Last Modified:29 Jul 2020 06:40
Publisher:The Company of Biologists
ISSN:0021-9533
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1242/jcs.209619
PubMed ID:29158223
Project Information:
  • : FunderFP7
  • : Grant ID256808
  • : Project TitleDIRECTFUEL - Direct biological conversion of solar energy to volatile hydrocarbon fuels by engineered cyanobacteria

Download

Hybrid Open Access

Download PDF  'TGF-β induces oncofetal fibronectin, which in turn modulates TGF-β superfamily signaling in endothelial cells'.
Preview
Content: Accepted Version
Filetype: PDF
Size: 1MB
View at publisher
Download PDF  'TGF-β induces oncofetal fibronectin, which in turn modulates TGF-β superfamily signaling in endothelial cells'.
Preview
Content: Published Version
Filetype: PDF
Size: 1MB