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Title: Matrix metalloproteinase-1 facilitates MSC migration via cleavage of IGF-2/IGFBP2 complex
Authors: Guan, S.P 
Lam, A.T.L
Newman, J.P
Chua, K.L.M
Kok, C.Y.L
Chong, S.T
Chua, M.L.K 
Lam, P.Y.P 
Keywords: gelatinase A
gelatinase B
interstitial collagenase
recombinant somatomedin B
somatomedin B
somatomedin binding protein 2
cell migration
concentration (parameters)
controlled study
human cell
in vitro study
mesenchymal stem cell
priority journal
protein cleavage
protein degradation
receptor blocking
signal transduction
Issue Date: 2018
Publisher: Wiley Blackwell
Citation: Guan, S.P, Lam, A.T.L, Newman, J.P, Chua, K.L.M, Kok, C.Y.L, Chong, S.T, Chua, M.L.K, Lam, P.Y.P (2018). Matrix metalloproteinase-1 facilitates MSC migration via cleavage of IGF-2/IGFBP2 complex. FEBS Open Bio 8 (1) : 15-26. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: The specific mechanism underlying the tumor tropism of human mesenchymal stem cells (MSCs) for cancer is not well defined. We previously showed that the migration potential of MSCs correlated with the expression and protease activity of matrix metalloproteinase (MMP)-1. Furthermore, highly tumor-tropic MSCs expressed higher levels of MMP-1 and insulin-like growth factor (IGF)-2 than poorly migrating MSCs. In this study, we examined the functional roles of IGF-2 and MMP-1 in mediating the tumor tropism of MSCs. Exogenous addition of either recombinant IGF-2 or MMP-1 could stimulate MSC migration. The correlation between IGF-2, MMP-1 expression, and MSC migration suggests that MMP-1 may play a role in regulating MSC migration via the IGF-2 signaling cascade. High concentrations of IGF binding proteins (IGFBPs) can inhibit IGF-stimulated functions by blocking its binding to its receptors and proteolysis of IGFBP is an important mechanism for the regulation of IGF signaling. We thus hypothesized that MMP-1 acts as an IGFBP2 proteinase, resulting in the cleavage of IGF-2/IGFBP2 complex and extracellular release of free IGF-2. Indeed, our results showed that conditioned media from highly migrating MSCs, which expressed high levels of MMP-1, cleaved the IGF-2/IGFBP2 complex. Taken together, these results showed that the MMP-1 secreted by highly tumor-tropic MSCs cleaved IGF-2/IGFBP2 complex. Free IGF-2 released from the complex may facilitate MSC migration toward tumor. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
Source Title: FEBS Open Bio
ISSN: 2211-5463
DOI: 10.1002/2211-5463.12330
Rights: Attribution 4.0 International
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