TABLE 3.
Location | Effects of Endostatin Binding | References | |
---|---|---|---|
Receptor | |||
VEGFR-2 (flk-1/KDR) | Blood vessel and lymphatic vessel surface | Inhibits angiogenesis by competitively inhibiting VEGFR-2. Prevents VEGF-C induced ERK/p38/MAPK signaling cascade. |
Pedram et al. [101] Kim et al. [102] |
VEGFR-3 (flt-4) | Lymphatic vessel surface | Inhibits lymphangiogenesis via direct and indirect mechanisms. | Han et al. [104] |
Integrin α5β1 | Cell surface | Disrupts cell migration. Causes integrin α5β1 to cluster and associate with caveolin-1. Causes phosphorylated Src to associate with caveolin-1 and disrupt focal adhesion factor and actin stress fibers. Hypothesized to prevent mast cells from binding to fibronectin. |
Wary et al. [113] Gille et al. [135] Rehn et al. [108] Wickstrom et al. [111] Sudhakar et al. [107] Morais et al. [112] Brideau et al. [136] |
Integrin αVβ3 | Cell surface | Inhibits angiogenesis. Hypothesized to prevent mast cell from binding to vitronectin. |
Rehn et al. [108] Brideau et al. [136] |
Glypican-1 and -4 | Blood vessel surface | Binding is necessary for endostatin to bind to its high-affinity receptor to elicit anti-angiogenic effects via unclear mechanism. | Karumanchi et al. [114] Reis et al. [116] |
Cell Surface-Associated Protein | |||
Thrombospondin-1 | ECM | Upregulates thrombospondin-1 expression | Abdollahi et al. [119] Faye et al. [117] |
SPARC | ECM | Unknown mechanism. | Abdollahi et al. [119] Faye et al. [117] |
Endorepellin | Blood vessel surface | Endorepellin inhibits endostatin’s anti-angiogenic activities, but carries out its own anti-angiogenic properties. | Miosge et al. [121] Mongiat et al. [120] |
Transglutaminase-2 | Blood vessel surface | Unknown mechanism. | Dardick [125] Faye et al. [117] Faye et al. [123] |
Biglycan | ECM | Prevents biglycan LDL retention and atheroma formation. | Zeng et al. [127] |
Amyloid Peptide | Brain | Implicated in Alzheimer’s disease. | Deininger et al. [128] Kranenburg et al. [129] Faye et al. [117] |
Nucleolin | Nucleolus | Inhibits cell migration and tube formation. | Srivastava et al. [137] Huang et al. [132] Shi et al. [134] |