Multiple angiogenesis stimulators in a single malignancy: implications for anti-angiogenic tumour therapy

Angiogenesis. 2001;4(4):259-62. doi: 10.1023/a:1016045012466.


Anti-angiogenesis is likely to develop into a novel therapeutic approach for patients with solid malignancies. Most current clinical trials evaluate anti-angiogenic drugs aimed primarily against single angiogenesis stimulators. Here, we show that a single solid malignancy, i.e., a human embryonal rhabdomyosarcoma, produces in vivo at least three biologically active angiogenesis stimulators (vascular endothelial growth factor, basic fibroblast growth factor and interleukin-8). This suggests that tumour angiogenesis results from the activity of multiple, rather than a single angiogenesis stimulator(s). We, furthermore, show that a combination of anti-angiogenic drugs is more effective in inhibiting tumour-induced endothelial cell growth than a single agent. Our results imply that clinical anti-angiogenic strategies for the treatment of solid malignancies may be most effective when multiple rather than single antiangiogenic drugs are used.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Cattle
  • Chromatography, Affinity
  • Endothelial Growth Factors / metabolism
  • Endothelial Growth Factors / physiology
  • Endothelium, Vascular / cytology
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / physiology
  • Humans
  • Interleukin-8 / metabolism
  • Interleukin-8 / physiology
  • Lymphokines / metabolism
  • Lymphokines / physiology
  • Neovascularization, Pathologic*
  • Urinary Bladder Neoplasms / blood supply*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Angiogenesis Inhibitors
  • Endothelial Growth Factors
  • Interleukin-8
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Fibroblast Growth Factor 2