Vijayan, A, Guha, D, Ameer, F et al. (9 more authors) (2013) IGFBP-5 enhances epithelial cell adhesion and protects epithelial cells from TGFβ1-induced mesenchymal invasion. International Journal of Biochemistry and Cell Biology, 45 (12). 2774 - 2785. ISSN 1357-2725
Abstract
TGFβ1 is a major fibrotic factor and its actions involve induction of epithelial cell death, together with the stimulation and transdifferentiation of fibroblasts into collagen- and fibronectin-secreting myofibroblasts. These actions of TGFβ1 are also consistent with a pro-metastatic role, by aiding epithelial cell escape through mesenchymal tissues. Recently IGFBP-5 has been described as a pro-fibrotic (pro-metastatic?) agent and the aim of this study was to compare and contrast the actions of IGFBP-5 with TGFβ1. We used NMuMG cells and cloned stable epithelial and mesenchymal lines from the parent cells. TGFβ1 induced apoptosis and/or EMT in the epithelial cells, whereas it enhanced mesenchymal cell survival and migration. IGFBP-5, in contrast, enhanced both cell-cell and cell-ECM adhesion and also improved wound closure in epithelial cells whereas, in mesenchymal cells, IGFBP-5 decreased adhesion and migration. Furthermore, IGFBP-5 was able to antagonise the actions of TGFβ1. In a co-culture model simulating epithelial-mesenchymal boundaries, IGFBP-5 was able to antagonise the disruptive transgressions induced by TGFβ1. Overall, these findings suggest that IGFBP-5 is important in maintaining epithelial-mesenchymal boundaries and thus may limit metastasis and fibrosis by inducing an orderly repair mechanism, very distinct from the fibrotic disruption induced by TGFβ1. A role for IGFBP-5 in the inhibition of metastasis is supported by immunohistochemical studies of breast cancer microarrays, where we show that elevated IGFBP-5 expression is associated with increased disease-free survival..
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2013 Elsevier B.V. NOTICE: this is the author’s version of a work that was accepted for publication in International Journal of Biochemistry and Cell Biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in International Journal of Biochemistry and Cell Biology, 45(12),(2013) DOI:10.1016/j.biocel.2013.10.001 |
Keywords: | Adhesion; Cancer; IGFBP-5; Migration; TGFβ1 |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Dentistry (Leeds) > Oral Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 24 Oct 2014 09:55 |
Last Modified: | 26 Jan 2018 04:32 |
Published Version: | http://dx.doi.org/10.1016/j.biocel.2013.10.001 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.biocel.2013.10.001 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:80795 |