TGF-ß induces oncofetal fibronectin that, in turn, modulates TGF-ß superfamily signaling in endothelial cells.
J Cell Sci
; 131(1)2018 01 09.
Article
em En
| MEDLINE
| ID: mdl-29158223
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 ß (TGF-ß) signaling has been attributed a pivotal role in glioblastoma, with TGF-ß 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. Ex vivo 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-ß signaling. Further, TGF-ß 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-ß superfamily signaling in endothelial cells via the EDA and EDB, pointing towards a bidirectional influence of oncofetal FN and TGF-ß superfamily signaling.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Fator de Crescimento Transformador beta
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Fibronectinas
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Células Endoteliais
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Cell Sci
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Suíça