VEGF receptors are differentially expressed by neuroblastoma cells in culture.
OBJECTIVE
Vascular endothelial growth factor (VEGF) is best known for its angiogenic properties, but its mitogenic capacity may be more important for tumorigenesis. The ability of VEGF to induce specific biologic activities may be dependent on the amount and type of VEGF receptors present. The authors hypothesize that neuroblastoma cells express specific VEGF receptors and that their expression may be altered when the cells are exposed to differing cytokines and culture environments.


METHODS
Four groups of human neuroblastoma cells (IMR-32) are studied. (1) Control cells: cultured in standard media. (2) VEGF cells: VEGF added to the media. (3) Tumor necrosis factor alpha (TNF-alpha) cells: TNF-alpha added to the media. (4) Serum starved cells: cultured in serum-depleted media. Reverse transcriptase polymerase chain reaction (RT-PCR) is utilized to measure the VEGF receptors flt-1, KDR/flk-1, flt-4, neuropilin 1 (NRP-1), and neuropilin 2 (NRP-2).


RESULTS
Flt-1 and KDR are not detected in any groups. Flt-4, NRP-1, and NRP-2 are present in the IMR-32 cells, and their expression is significantly increased by the administration of VEGF. Neuroblastoma cells cultured with TNF-alpha or in serum-depleted media have a significant decrease in the expression of these receptors.


CONCLUSIONS
The authors show that neuroblastoma cells express specific VEGF receptors that may be altered by mitogenic or apoptotic stimuli. Specifically targeting VEGF and its receptors may be another therapeutic strategy for the treatment of neuroblastoma.
Beierle
Elizabeth A
EA
Department of Surgery, University of Florida, J. Hillis Miller Health Science Center, Gainesville, Florida 32610-0286, USA.
Dai
Wei
W
Langham
Max R
MR
Copeland
Edward M
EM
Chen
Mike K
MK
D016895:Culture Media, Serum-Free; D004730:Endothelium, Vascular / Q000187:drug effects / Q000196:embryology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D039942:Neuropilin-1 / Q000096:biosynthesis / Q000235:genetics; D039943:Neuropilin-2 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000096:biosynthesis / Q000235:genetics
D016895:Culture Media, Serum-Free; D009363:Neoplasm Proteins; D039943:Neuropilin-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D039942:Neuropilin-1; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3