Targeting the anthrax receptors, TEM-8 and CMG-2, for anti-angiogenic therapy

Front Biosci (Landmark Ed). 2011 Jan 1;16:1574-88. doi: 10.2741/3806.

Abstract

The anthrax toxin receptors tumor endothelial marker-8 (TEM-8) and capillary morphogenesis gene-2 (CMG-2) are responsible for allowing entry of anthrax toxin into host cells. These receptors were first discovered due to their enhanced expression on endothelial cells undergoing blood vessel growth or angiogenesis in model systems. Inhibition of angiogenesis is an important strategy for current anti-cancer therapies and treatment of retinal diseases. Functional roles for TEM-8 and CMG-2 in angiogenesis have recently emerged. TEM-8 appears to regulate endothelial cell migration and tubule formation whereas a role for CMG-2 in endothelial proliferation has been documented. TEM-8 and CMG-2 bind differentially to extracellular matrix proteins including collagen I, collagen IV and laminin and these properties may be responsible for their apparent roles in regulating endothelial cell behavior during angiogenesis. TEM-8-binding moieties have also been suggested to be useful in selectively targeting anti-angiogenic and anti-tumorigenic therapies to tumor endothelium. Additionally, studies of modified forms of lethal toxin (LeTx) have demonstrated that targeted inhibition of MAPKs within tumor vessels may represent an efficacious anti-angiogenic strategy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antigens, Bacterial / metabolism*
  • Antigens, Bacterial / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Bacterial Toxins / metabolism*
  • Bacterial Toxins / therapeutic use
  • Endothelial Cells / physiology
  • Extracellular Matrix / metabolism
  • Humans
  • Membrane Proteins / drug effects*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microfilament Proteins
  • Neoplasm Proteins / drug effects*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neovascularization, Pathologic / drug therapy*
  • Receptors, Cell Surface / drug effects*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Peptide

Substances

  • ANTXR1 protein, human
  • ANTXR2 protein, human
  • Angiogenesis Inhibitors
  • Antigens, Bacterial
  • Antineoplastic Agents
  • Bacterial Toxins
  • Membrane Proteins
  • Microfilament Proteins
  • Neoplasm Proteins
  • Receptors, Cell Surface
  • Receptors, Peptide
  • anthrax toxin