Expression of vascular endothelial growth factor (VEGF) and VEGF receptors in human neuroblastomas

Med Pediatr Oncol. 2000 Jun;34(6):386-93. doi: 10.1002/(sici)1096-911x(200006)34:6<386::aid-mpo2>;2-3.


Background: Vascular endothelial growth factor (VEGF) is a specific endothelial cell mitogen that stimulates angiogenesis and plays a crucial role in tumor growth. The aim of the present study was to evaluate the expression of VEGF and of its two high-affinity tyrosine kinase receptors (KDR and Flt-1) in neuroblastoma surgical samples and cell lines.

Procedure: The VEGF, KDR, and Flt-1 mRNA expression in neuroblastoma surgical samples and cell lines was studied by RT-PCR. The receptors were identified in [(125)I]VEGF binding and in functional studies (effect on cell growth). VEGF production by neuroblastomas was investigated by the ELISA method.

Results: It was possible to observe the mRNAs encoding for VEGF and its two receptors in some of the surgical specimens examined, including most of the high-grade tumors. It was also possible to demonstrate that the SK-N-BE cell line expressed VEGF, KDR, and Flt-1 mRNAs as well as biologically active receptors: The cells bound [(125)I]-VEGF, and their growth was stimulated by exogenous VEGF. Moreover, VEGF protein could be detected in their culture conditioned medium.

Conclusions: These results suggest that, in addition to its effect on angiogenesis, VEGF may affect neuroblastoma cell growth directly and could be an autocrine growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • DNA, Neoplasm / biosynthesis
  • Endothelial Growth Factors / biosynthesis*
  • Endothelial Growth Factors / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Infant
  • Lymphokines / biosynthesis*
  • Lymphokines / genetics
  • Male
  • Neuroblastoma / metabolism*
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • RNA
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis
  • Receptor Protein-Tyrosine Kinases / biosynthesis*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptors, Growth Factor / biosynthesis*
  • Receptors, Growth Factor / genetics
  • Receptors, Mitogen / biosynthesis*
  • Receptors, Mitogen / genetics
  • Receptors, Vascular Endothelial Growth Factor
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factors


  • DNA, Neoplasm
  • Endothelial Growth Factors
  • Lymphokines
  • Proto-Oncogene Proteins
  • RNA primers
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Growth Factor
  • Receptors, Mitogen
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • RNA
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1