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Tissue inhibitor of metalloproteinases‐2 inhibits bFGF‐induced human microvascular endothelial cell proliferation
Author(s) -
Murphy Anne N.,
Unsworth Edward J.,
StetlerStevenson William G.
Publication year - 1993
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041570219
Subject(s) - angiogenesis , cell growth , endothelial stem cell , basic fibroblast growth factor , matrix metalloproteinase , gelatinase , tissue inhibitor of metalloproteinase , cell culture , collagenase , chemistry , microbiology and biotechnology , biology , in vitro , growth factor , biochemistry , cancer research , enzyme , receptor , genetics
Tissue inhibitor of metalloproteinase‐2 (TIMP‐2), a protease inhibitor that binds to the latent and active forms of 72 kDa type IV collagenase (gelatinase A), was found to inhibit the in vitro proliferation of human microvascular endothelial (HME) cells stimulated with bFGF and 5% serum. The maximal inhibitory effect of TIMP‐2 on incorporation of 3 H‐thymidine was evident 24 hours after bFGF stimulation of these cells and ranged between 45 and 60%. The half‐maximal effective concentration of TIMP‐2 was 107 ± 12 nM (S.D.). In contrast, TIMP‐1 was not found to slow the growth of HME cells. The inhibition of cell proliferation observed with TIMP‐2 was not mimicked by addition to the culture medium of BB94, a general matrix metalloproteinase inhibitor, nor antibodies to the 72 kDa type IV collagenase. In addition to growth, two other cell functions associated with the angiogenic process were tested for sensitivity to TIMP‐2. Cell adhesion to tissue culture platic was slightly stimulated by TIMP‐2, and cell migration was inhibited with short‐term exposure to TIMP‐2, but neither process was affected by longer‐term exposure. The ability of TIMP‐2 to inhibit cultured endothelial cell proliferation independent of protease inhibitory activity suggests that TIMP‐2 may have additional actions which may limit neovascularization associated with solid tumor growth and metastasis in vivo. © 1993 Wiley‐Liss, Inc.