TGF-β induces oncofetal fibronectin, which in turn modulates TGF-β superfamily signaling in endothelial cells
| Autor: | Luciano Zardi, Elisa Ventura, Manfred Claassen, Cinzia Cordazzo, Isabel Burghardt, Christian Beisel, Will Macnair, Katja Eschbach, Michael Weller |
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| Přispěvatelé: | University of Zurich, Burghardt, Isabel |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CD31 Vascular smooth muscle Angiogenesis Population Cell 610 Medicine & health 1307 Cell Biology 03 medical and health sciences Transforming Growth Factor beta TGF beta signaling pathway medicine Humans Protein Isoforms RNA Messenger education Cells Cultured education.field_of_study biology Neovascularization Pathologic Gene Expression Profiling Endothelial Cells Cell Biology Cell biology Fibronectins 10040 Clinic for Neurology Fibronectin Alternative Splicing 030104 developmental biology medicine.anatomical_structure Immunology biology.protein Transforming growth factor Signal Transduction |
| DOI: | 10.5167/uzh-142506 |
| Popis: | 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. 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-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. |
| Databáze: | OpenAIRE |
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