Open AccessMatrix metalloproteinase‐1 facilitates MSC migration via cleavage of IGF ‐2/ IGFBP 2 complex
Author(s) -
Guan Shou P.,
Lam Alan T.L.,
Newman Jennifer P.,
Chua Kevin L.M.,
Kok Catherine Y.L.,
Chong Siao T.,
Chua Melvin L.K.,
Lam Paula Y.P.
Publication year - 2018
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12330
Subject(s) - matrix metalloproteinase , growth factor , microbiology and biotechnology , chemistry , extracellular matrix , cleavage (geology) , mesenchymal stem cell , receptor , cell migration , proteolysis , biology , biochemistry , cell , enzyme , paleontology , fracture (geology)
The specific mechanism underlying the tumor tropism of human mesenchymal stem cells ( MSC s) for cancer is not well defined. We previously showed that the migration potential of MSC s correlated with the expression and protease activity of matrix metalloproteinase ( MMP )‐1. Furthermore, highly tumor‐tropic MSC s expressed higher levels of MMP ‐1 and insulin‐like growth factor ( IGF )‐2 than poorly migrating MSC s. In this study, we examined the functional roles of IGF ‐2 and MMP ‐1 in mediating the tumor tropism of MSC s. 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 ( IGFBP s) 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 IGFBP 2 proteinase, resulting in the cleavage of IGF ‐2/ IGFBP 2 complex and extracellular release of free IGF ‐2. Indeed, our results showed that conditioned media from highly migrating MSC s, which expressed high levels of MMP ‐1, cleaved the IGF ‐2/ IGFBP 2 complex. Taken together, these results showed that the MMP ‐1 secreted by highly tumor‐tropic MSC s cleaved IGF ‐2/ IGFBP 2 complex. Free IGF ‐2 released from the complex may facilitate MSC migration toward tumor.