Table 2 |
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Endogenous angiogenesis inhibitors |
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Inhibitor |
Molecular and physiologic properties |
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Proteolytic fragments |
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Angiostatin |
38-kD internal fragment of plasminogen (kringles 1-4); kringles 1-3 and kringle 5 also active. |
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Arrestin |
26-kD carboxy-terminal noncollagenous domain of a1 chain of Type IV collagen; inhibits endothelial cell (EC) proliferation. |
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Antithrombin (cleaved) |
53-55-kD cleaved conformation inhibits EC proliferation and tumor growth in mice. |
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Canstatin |
24-kD carboxy-terminal noncollagenous domain of a2 chain of Type IV collagen; inhibits EC proliferation and apoptosis. |
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Endostatin |
20-kD fragment of carboxy-terminal noncollagenous domain of Type XVIII collagen; mechanism of action unknown. |
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Fibronectin fragments |
29-kD amino-terminal and 40-kD carboxy-terminal heparin-binding fragments inhibit EC proliferation. |
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PEX |
Carboxy-terminal hemopexin-like domain of matrix metalloproteinase-2 inhibits EC proliferation and tumor growth in mice. |
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Prolactin (16-kD) |
Naturally occurring 16-kD cleaved amino-terminal fragment of prolactin; retains activity as partial prolactin agonist. |
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Prothrombin kringle-2 |
22-kD prothrombin fragment initially isolated from lipopolysaccharide-treated serum. |
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Restin |
22-kD fragment of carboxy-terminal noncollagenous domain of Type XV collagen; 60% homology to murine endostatin. |
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Vasostatin |
Amino-terminal fragment of calreticulin; inhibits EC proliferation and tumor growth in mice. |
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Interleukins |
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IL-1 |
17-kD β-isoform inhibits FGF-stimulated angiogenesis by an autocrine pathway. |
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IL-4 |
13-kD lymphokine; inhibits basic FGF-induced angiogenesis. |
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IL-10 |
Inhibits tumor vascularity and growth, possibly by decreasing macrophage-derived angiogenic factors. |
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IL-12 |
75-kD glycoprotein; inhibits in vivo angiogenesis via IFN-γ - and IP-10-related mechanism. |
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IL-18 |
IFN-γ-inducing cytokine; inhibits FGF-stimulated EC proliferation and in vivo angiogenesis. |
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Interferons |
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IFN-α |
8 to 20-kD glycoproteins secreted by lymphocytes and phagocytes; inhibits EC proliferation and migration. |
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IFN-β |
23-kD glycoprotein derived from fibroblasts and epithelial cells. |
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IFN-γ |
20 to 25-kD glycoprotein secreted by T cells and natural killer cells; cytotoxic to proliferating ECs. |
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TIMP metallopeptidase inhibitors |
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TIMP-1 (TIMP metallo-peptidase inhibitor 1) |
Soluble 8.5-kD collagenase inhibitor. |
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TIMP-2 |
Soluble 21-kD collagenase inhibitor. |
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TIMP-3 |
Extracellular matrix-associated collagenase inhibitor. |
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Other molecules |
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1,25-(OH)2-vitamin D3 |
Antiangiogenic effect similar to that of retinoic acid; nonhydroxylated vitamin D3 not active. |
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2-methoxyestradiol |
0.3-kD estrogen metabolite; inhibits EC migration and urokinase plasminogen activator. |
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Angiopoietin-2 |
Inhibits angiopoietin-1-mediated activation of EC tyrosine kinase receptor, Tie2; role in vascular remodeling. |
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EMAP-II |
Tumor-derived 20-kD (34 kD proform) inflammatory cytokine. |
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Gro-β |
8-kD CXC chemokine; inhibits tumor growth in mice. |
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IP-10 |
8.6-kD CXC chemokine induced by IFNγ -. |
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Maspin |
42-kD serine protease inhibitor (serpin); inhibits EC migration and tumor growth and vascularity in mice. |
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METH-1, METH-2 |
110- and 98-kD proteins with metalloprotease and disintegrin-like domains, and carboxy-terminal type 1 TSP-1 repeats. |
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MIG |
11.7-kD CXC chemokine induced by IFN-γ. |
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p16 |
Tumor supressor gene; wild type downregulates VEGF expression and inhibits angiogenesis in gliomas. |
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p53 |
Tumor suppressor gene; wild type increases TSP-1 expression, decreases VEGF expression. |
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PEDF |
50-kD inhibitor expressed by retinal pigment epithelial cells. |
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Platelet factor-4 |
28-kD heparin-binding platelet-derived inhibitory factor. |
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Proliferin-related protein |
Inhibitor of placental angiogenesis in late gestation. |
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Prostate-specific antigen |
Serine protease associated with prostate carcinoma and other tumors. |
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Protamine |
43-kD heparin-binding protein produced by sperm; role in vessel remodeling. |
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Retinoic acid |
0.3-kD inhibitor of EC migration; appears to act as transcriptional regulator. |
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Soluble FGF receptor |
60 to 85-kD circulating binding proteins that may regulate pro-angiogenic activity of FGF. |
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Transforming growth factor β1 |
25-kD inhibitor of EC growth and proteolytic activity. |
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Troponin I |
Subunit of troponin complex recently found to be present in cartilage and to inhibit angiogenesis. |
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TSP-1, TSP-2 |
450-kD platelet- and fibroblast-derived trimeric glycoproteins. |
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Burton and Libutti Journal of Biology 2009 8:85 doi:10.1186/jbiol189 |
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