TABLE 3.

A summary of the receptors that endostatin binds to and its subsequent effects.

	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]