Importance of vascular endothelial growth factor A in the progression of experimental neuroblastoma.
Vascular endothelial growth factor A (VEGF-A) and its receptor tyrosine kinases located on endothelial cells seem to play an important role in the multistep pathway of angiogenesis. SU5416 is a small molecule which inhibits angiogenesis by acting as an inhibitor of VEGF receptor-2 tyrosine kinase. We have developed a reproducible murine model for neuroblastoma, a childhood cancer, based on s.c. xenotransplantation of SH-SY5Y neuroblastoma cells. We found that SH-SY5Y cells expressed VEGF-A on both the mRNA and protein levels, that plasma concentrations of VEGF-A were significantly elevated in animals with neuroblastoma with a volume > 1.4 ml, and that there was a correlation between VEGF-A levels in plasma and tumor size in untreated tumor-bearing animals. Treatment with SU5416 reduced the growth of neuroblastoma tumors by 65% without apparent toxicity. SU5416 treatment also suppressed tumor angiogenesis, despite an increase in plasma VEGF-A levels per ml tumor volume during therapy. Our experimental data suggest that the angiogenesis inhibitor SU5416 may be beneficial in the treatment of solid tumors of childhood such as neuroblastoma.
Bäckman
Ulrika
U
Department of Medical Cell Biology, Children's Hospital, Uppsala University, Sweden. ulrika.backman@medcellbiol.uu.se
Svensson
Asa
A
Christofferson
Rolf
R
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000097:blood / Q000502:physiology*; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D009447:Neuroblastoma / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A
D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D007211:Indoles; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; C116890:Semaxinib; D011505:Protein-Tyrosine Kinases