Selective upregulation of vascular endothelial growth factor receptors neuropilin-1 and -2 in human neuroblastoma.
BACKGROUND
Recent studies show that vascular endothelial growth factor (VEGF) and its receptors Flt-1 and KDR, and a series of other angiogenic molecules, are upregulated in advanced but not low stage human neuroblastoma. Neuropilin-1 and 2 (NRP) are novel specific receptors of VEGF(165), whose role is unknown in human neuroblastoma.


METHODS
Tissue biopsies of 37 children with Stage I-IV neuroblastoma were obtained, as well as biopsies of 7 normal adrenals as controls. The mRNA expression of VEGF(165) and its receptors Flt-1, KDR, NRP1, and NRP2 was evaluated by real-time reverse transcription polymerase chain reaction. NRP protein expression was detected by immunocytochemistry and Western blotting.


RESULTS
VEGF(165) mRNA was upregulated in Stage III and IV and Flt-1 and KDR gene expression was increased in Stage III, while NRP1 and 2 mRNA and protein levels were higher in Stages I-IV vs. controls (P < 0.05). NRP was expressed in vascular endothelial but not tumor cells.


CONCLUSIONS
These results show for the first time that human neuroblastoma expresses NRP, and that NRP co-regulates VEGF angiogenic effect in human neuroblastoma. NRP might be a sensitive angiogenic measure of VEGF systems in neuroblastoma, particularly in its early stages.
Fakhari
Mitra
M
Department of Pediatric Surgery, University of Vienna, Vienna, Austria.
Pullirsch
Dieter
D
Abraham
Dietmar
D
Paya
Kurosh
K
Hofbauer
Reinhold
R
Holzfeind
Paul
P
Hofmann
Michael
M
Aharinejad
Seyedhossein
S
D015153:Blotting, Western; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D039942:Neuropilin-1; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D039942:Neuropilin-1; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor