Hemers, E, Duval, C, McCaig, C et al. (3 more authors) (2005) Insulin-like growth factor binding protein-5 is a target of matrix metalloproteinase-7: implications for epithelial-mesenchymal signaling. Cancer Research, 65 (16). 7363 - 7369. ISSN 0008-5472
Abstract
Matrix metalloproteinase-7 (MMP-7) is localized to epithelial cells and is up-regulated in many cancers and in inflammation. We now report that MMP-7 targets a key mesenchymal cell type, the myofibroblast. Recombinant MMP-7 stimulated the proliferation and migration of human colonic myofibroblasts. These responses were partly attributable to activation of other MMPs, notably MMP-3 and MMP-8, and to stimulation of the mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways. Using a proteomic approach, we identified insulin-like growth factor binding protein-5 (IGFBP-5) as a previously unsuspected target of MMP-7 produced by colonic myofibroblasts. We present evidence that the MMP-7 cleavage of IGFBP-5 liberates IGF-II that functions as an autocrine myofibroblast growth factor. Thus, MMP-7 may act as a signal from epithelial cells for local recruitment of myofibroblasts and stimulation of their proliferation. Similar effects of MMP-7 produced in epithelial tumors might account for the expansion of stroma through activation of myofibroblasts.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Amino acid sequence; cell growth processes; cell movement; colon; epithelial cells; fibroblasts; humans; insulin-like growth factor binding protein 5; insulin-like growth factor II; MAP kinase signaling system; matrix metalloproteinase 7; mesoderm; molecular sequence data; phosphatidylinositol 3-kinases |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Genetics, Health and Therapeutics (LIGHT) > Academic Unit of Cardiovascular Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 27 Mar 2015 11:45 |
Last Modified: | 03 Nov 2016 17:39 |
Published Version: | http://dx.doi.org/10.1158/0008-5472.CAN-05-0157 |
Status: | Published |
Publisher: | American Association for Cancer Research |
Identification Number: | 10.1158/0008-5472.CAN-05-0157 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:83630 |