| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on May 23, 2003
Accepted on October 28, 2003
1 Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, AR 72202; Department of Pediatrics, Duke University Medical Center, Durham, NC, 27710; Department of Molecular and Structural Biology, University of Arhus, Gustav Wieds Vej 10C, Aarhus, Denmark; and Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 1 Aspenlea Rd, London W6 8LH, UK.
* To whom correspondence should be addressed. E-mail: fowlkesjohnl{at}uams.
Insulin-like growth factors (IGF-I and IGF-II) play important roles in growth and development via interactions with cell-surface receptors; however, in nature, IGFs are sequestered by at least six soluble, high-affinity IGF-binding proteins (IGFBPs 1-6). Herein we demonstrate that the stromal cell-derived extracellular matrix-degrading metalloproteinase stromelysin 1 (matrix metalloproteinase 3) disrupts IGF/IGFBP-3 complexes and liberates free, intact IGFs, leading to phosphorylation of cell surface type 1 IGF receptors and cellular proliferation. Tissue inhibitor of metalloproteinases (TIMP-1) or an antibody to the type 1 IGF receptor mitigates IGF-mediated cellular proliferation. Thus, these studies suggest that MMPs, beyond their effects on extracellular matrix turnover, regulate cellular proliferation by modulating the bioavailability of IGFs, an event critical for such diverse phenomena as embryo development, morphogenesis, angiogenesis and tumorigenesis.
This article has been cited by other articles:
 |
|
 |
|
  P. H. Larsen, A. G. DaSilva, K. Conant, and V. W. Yong Myelin formation during development of the CNS is delayed in matrix metalloproteinase-9 and -12 null mice. J. Neurosci., February 22, 2006; 26(8): 2207 - 2214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ii, H. Yamamoto, Y. Adachi, Y. Maruyama, and Y. Shinomura Role of Matrix Metalloproteinase-7 (Matrilysin) in Human Cancer Invasion, Apoptosis, Growth, and Angiogenesis Experimental Biology and Medicine, January 1, 2006; 231(1): 20 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Stephens, P. McElduff, A. H. Heald, J. P. New, J. Worthington, W. E. Ollier, and J. M. Gibson Polymorphisms in IGF-Binding Protein 1 Are Associated With Impaired Renal Function in Type 2 Diabetes Diabetes, December 1, 2005; 54(12): 3547 - 3553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ogawa, T. Nikawa, H. Furochi, M. Kosyoji, K. Hirasaka, N. Suzue, K. Sairyo, S. Nakano, T. Yamaoka, M. Itakura, et al. Osteoactivin upregulates expression of MMP-3 and MMP-9 in fibroblasts infiltrated into denervated skeletal muscle in mice Am J Physiol Cell Physiol, September 1, 2005; 289(3): C697 - C707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Hemers, C. Duval, C. McCaig, M. Handley, G. J. Dockray, and A. Varro Insulin-Like Growth Factor Binding Protein-5 Is a Target of Matrix Metalloproteinase-7: Implications for Epithelial-Mesenchymal Signaling Cancer Res., August 15, 2005; 65(16): 7363 - 7369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Gharib, D. L. Luchtel, D. K. Madtes, and R. W. Glenny Global gene annotation analysis and transcriptional profiling identify key biological modules in hypoxic pulmonary hypertension Physiol Genomics, June 16, 2005; 22(1): 14 - 23. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
