Inhibition of angiogenesis by tissue inhibitor of metalloproteinase

Authors

  • Mark D. Johnson,

    Corresponding author
    1. Departments of Pathology, Northwestern University Medical School, and Lurie Cancer Center, Chicago, Illinois 60611
    • The Department of Pathology, Olson-8317, 745 N. Fairbanks, Chicago, IL 60611
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  • Dr. Hyeong-Reh Choi Kim,

    1. Departments of Pathology, Northwestern University Medical School, and Lurie Cancer Center, Chicago, Illinois 60611
    Current affiliation:
    1. The Department of Pathology, Wayne State University, Detroit, MI 48201
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  • Louis Chesler,

    1. Departments of Pathology, Northwestern University Medical School, and Lurie Cancer Center, Chicago, Illinois 60611
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  • Gladys Tsao-Wu,

    1. Departments of Pathology, Northwestern University Medical School, and Lurie Cancer Center, Chicago, Illinois 60611
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  • Dr. Peter J. Polverini,

    1. Departments of Pathology, Northwestern University Medical School, and Lurie Cancer Center, Chicago, Illinois 60611
    Current affiliation:
    1. The School of Dentistry, University of Michigan, Ann Arbor, MI 48109
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  • Noel Bouck

    1. Microbiology/Immunology, Northwestern University Medical School, and Lurie Cancer Center, Chicago, Illinois 60611
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Abstract

Matrix proteases play a critical role in cell invasion and migration, including the process of angiogenesis. The ability of specific factors to induce angiogenic responses correlates with their stimulation of matrix protease synthesis and release. Using an in vivo angiogenesis assay, the endothelial cell response to known angiogenic factors, basic fibroblast growth factor (bfGF) and adipocyte conditioned medium, was blocked by an inhibitor of matrix metalloproteinase activity, TIMP-1. The TIMP effect was mediated, at least in part, through the inhibition of endothelial cell migration, as determined by the ability of TIMP to block chemotaxis in a Boyden chamber assay. These results indicate that the inhibition of migration is a direct effect on the endothelial cells and does not require accessory cells. An additional observation was that the RNA levels for TIMP were significantly reduced in differentiated adipocytes, compared to undifferentiated F442A controls. Therefore, the acquisition of an angiogenic phenotype may involve not only the induction of positive factors, but also the suppression of angiogenesis inhibitors. © 1994 Wiley-Liss, Inc.

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