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