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


METHODS
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.
Langer
I
I
Department of Pharmacology, Institute of Pharmacy, Université Libre de Bruxelles, Brussels, Belgium.
Vertongen
P
P
Perret
J
J
Fontaine
J
J
Atassi
G
G
Robberecht
P
P
D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000096:biosynthesis; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D009447:Neuroblastoma / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D012313:RNA; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D017978:Receptors, Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D011975:Receptors, Mitogen / Q000096:biosynthesis* / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D004273:DNA, Neoplasm; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; C034477:RNA primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017978:Receptors, Growth Factor; D011975:Receptors, Mitogen; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D012313:RNA; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1