Importance of vascular endothelial growth factor A in the progression of experimental neuroblastoma.

Abstract

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.

• Authors: Ulrika Bäckman, Asa Svensson, Rolf Christofferson
• Journal: Angiogenesis (Angiogenesis) Vol. 5 Issue 4 Pg. 267-74 ( 2002) ISSN: 0969-6970 [Print] Germany
• PMID: 12906318 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Endothelial Growth Factors
• Indoles
• Pyrroles
• Vascular Endothelial Growth Factor A
• Semaxinib
• Protein-Tyrosine Kinases

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Cell Division (drug effects)
• Endothelial Growth Factors (blood, physiology)
• Female
• Humans
• Indoles (pharmacology)
• Male
• Mice
• Mice, Nude
• Neoplasms, Experimental (drug therapy, etiology, metabolism)
• Neuroblastoma (drug therapy, etiology, metabolism)
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Pyrroles (pharmacology)
• Transplantation, Heterologous
• Tumor Cells, Cultured
• Vascular Endothelial Growth Factor A