Selective blockade of tumor angiogenesis

Cell Cycle. 2012 Jun 15;11(12):2253-9. doi: 10.4161/cc.20374. Epub 2012 Jun 15.


Blocking tumor angiogenesis is an important goal of cancer therapy, but clinically approved anti-angiogenic agents suffer from limited efficacy and adverse side effects, fueling the need to identify alternative angiogenesis regulators. Tumor endothelial marker 8 (TEM8) is a highly conserved cell surface receptor overexpressed on human tumor vasculature. Genetic disruption of Tem8 in mice revealed that TEM8 is important for promoting tumor angiogenesis and tumor growth but dispensable for normal development and wound healing. The induction of TEM8 in cultured endothelial cells by nutrient or growth factor deprivation suggests that TEM8 may be part of a survival response pathway that is activated by tumor microenvironmental stress. In preclinical studies, antibodies targeted against the extracellular domain of TEM8 inhibited tumor angiogenesis and blocked the growth of multiple human tumor xenografts. Anti-TEM8 antibodies augmented the activity of other anti-angiogenic agents, vascular targeting agents and conventional chemotherapeutic agents and displayed no detectable toxicity. Thus, anti-TEM8 antibodies provide a promising new tool for selective blockade of neovascularization associated with cancer and possibly other angiogenesis-dependent diseases.

Publication types

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

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibodies / therapeutic use
  • Biomarkers, Tumor / deficiency
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cells, Cultured
  • Endothelial Cells / metabolism
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Knockout
  • Microfilament Proteins
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neovascularization, Pathologic*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Peptide / deficiency
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism
  • Transfection
  • Transplantation, Heterologous


  • ANTXR1 protein, human
  • Antibodies
  • Antxr1 protein, mouse
  • Antxr2 protein, mouse
  • Biomarkers, Tumor
  • Microfilament Proteins
  • Neoplasm Proteins
  • Receptors, Cell Surface
  • Receptors, Peptide