The role of thymidine phosphorylase, an angiogenic enzyme, in tumor progression

Cancer Sci. 2004 Nov;95(11):851-7. doi: 10.1111/j.1349-7006.2004.tb02193.x.


Thymidine phosphorylase (TP), an enzyme involved in pyrimidine metabolism, is identical with an angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF). TP is overexpressed in various tumors and plays an important role in angiogenesis, tumor growth, invasion and metastasis. The enzymatic activity of TP is required for the angiogenic effect of TP. A novel, specific TP inhibitor, TPI, inhibits angiogenesis induced by overexpression of TP in KB/TP cells (human KB epidermoid carcinoma cells transfected with TP cDNA), as well as the growth and metastasis of KB/TP cells in vivo. 2-deoxy-D-ribose, the degradation product of thymidine generated by TP activity, has both angiogenic and chemotactic activity. Both 2-deoxy-D-ribose and TP inhibit a hypoxia-induced apoptotic pathway. These findings suggest that 2-deoxy-D-ribose is a downstream mediator of TP function. 2-deoxy-L-ribose, a stereoisomer of 2-deoxy-D-ribose, inhibits the promotion of angiogenesis, tumor growth and metastasis by TP. Although the mechanism of the action of 2-deoxy-D-ribose is still unknown, 2-deoxy-L-ribose may inhibit the physiological activities of 2-deoxy-D-ribose, and consequently those of TP. Inhibition of TP activity and function appears to be a promising approach for the chemotherapy of various tumors.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inducing Agents / pharmacology
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Deoxyribose / metabolism
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasms / enzymology*
  • Neovascularization, Pathologic / enzymology*
  • Thymidine / metabolism
  • Thymidine Phosphorylase / antagonists & inhibitors
  • Thymidine Phosphorylase / physiology*


  • Angiogenesis Inducing Agents
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Deoxyribose
  • Thymidine Phosphorylase
  • Thymidine