Multiple angiogenesis stimulators in a single malignancy: implications for anti-angiogenic tumour therapy.
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.
Pavlakovic
H
H
Department of Hematology/Oncology and Endocrinology, Children's Hospital, University of Essen, Hufelandstr. 55, 45122 Essen, Germany.
Havers
W
W
Schweigerer
L
L
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002417:Cattle; D002846:Chromatography, Affinity; D016228:Endothelial Growth Factors / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism / Q000502:physiology; D008222:Lymphokines / Q000378:metabolism / Q000502:physiology; D009389:Neovascularization, Pathologic; D001749:Urinary Bladder Neoplasms / Q000098:blood supply*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D016209:Interleukin-8; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2