IGFBP-5 enhances epithelial cell adhesion and protects epithelial cells from TGFβ1-induced mesenchymal invasion
Vijayan, A and Guha, D and Fasal, A and Kaziri, I and Mooney, C C and Bennett, L and Sureshbabu, A and Tonner, E and Beattie, J and Edwards, J and Flint, D J (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). pp. 2774-2785.
![]() |
PDF (Vijayan et al International Journal of Biochemistry and Cell Biology 2013)
VijayanetalBiocel2013.pdf Final Published Version License: ![]() Download (3MB) |
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.
Creators(s): |
Vijayan, A, Guha, D, Fasal, A, Kaziri, I, Mooney, C C ![]() | Item type: | Article |
---|---|
ID code: | 45833 |
Notes: | Copyright © 2013. Published by Elsevier Ltd. |
Keywords: | breast cancer , boundaries, IGFBP-5, TGF1, adhesion, migration, Therapeutics. Pharmacology, Neoplasms. Tumors. Oncology (including Cancer), Pharmacology (medical), Cancer Research |
Subjects: | Medicine > Therapeutics. Pharmacology Medicine > Internal medicine > Neoplasms. Tumors. Oncology (including Cancer) |
Department: | Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences |
Depositing user: | Pure Administrator |
Date deposited: | 12 Nov 2013 14:07 |
Last modified: | 20 Jan 2021 20:56 |
Related URLs: | |
URI: | https://strathprints.strath.ac.uk/id/eprint/45833 |
Export data: |