IGFBP-5 enhances epithelial cell adhesion and protects epithelial cells from TGF beta 1-induced mesenchymal invasion

TGF beta 1 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 TGF beta 1 are also consistent with a pro-metastatic role,...

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Bibliographic Details
Published in:The international journal of biochemistry & cell biology 2013-12, Vol.45 (12), p.2774-2785
Main Authors: Vijayan, A, Guha, D, Ameer, F, Kaziri, I, Mooney, C C, Bennett, L, Sureshbabu, A, Tonner, E, Beattie, J, Allan, G J, Edwards, J, Flint, D J
Format: Article
Language:English
Subjects:
Adhesion
Boundaries
Breast
Cell adhesion
Computer simulation
Fibrosis
Migration
Survival
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Summary:TGF beta 1 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 TGF beta 1 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 TGF beta 1. We used NMuMG cells and cloned stable epithelial and mesenchymal lines from the parent cells. TGF beta 1 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 TGF beta 1. In a co-culture model simulating epithelial-mesenchymal boundaries, IGFBP-5 was able to antagonise the disruptive transgressions induced by TGF beta 1. 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 TGF beta 1. 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.
ISSN:1357-2725
DOI:10.1016/j.biocel.2013.10.001