Expression of neurotrophin receptor TrkA inhibits angiogenesis in neuroblastoma.
BACKGROUND
Mechanisms regulating the expression of angiogenic factors in tumor cells are largely unknown. High expression of the neurotrophin receptor TrkA in neuroblastomas (NB) is associated with favorable prognosis, whereas TrkB is expressed on aggressive, MYCN-amplified NB.


METHODS
To investigate the biological effects of TrkA and TrkB expression on angiogenesis in NB, we examined the expression of angiogenic factors in the human NB cell line SY5Y and its TrkA and TrkB transfectants.


RESULTS
In comparison to parental SY5Y cells, mRNA and protein levels of angiogenic factors were significantly reduced in SY5Y-TrkA cells, whereas SY5Y-TrkB cells did not demonstrate a significant change. Conditioned medium (CM) of parental SY5Y and SY5Y-TrkB cells induced endothelial cell proliferation, but this effect was completely absent in SY5Y-TrkA cells. TrkA expression also resulted in severely impaired tumorigenicity in a mouse xenograft model, and was associated with reduced angiogenic factor expression and less vascularization of tumors, as determined by immunohistochemistry and an in vivo Matrigel assay.
Eggert
A
A
Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Grotzer
M A
MA
Ikegaki
N
N
Liu
X G
XG
Evans
A E
AE
Brodeur
G M
GM
D002455:Cell Division; D016228:Endothelial Growth Factors / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006801:Humans; D008222:Lymphokines / Q000502:physiology; D009389:Neovascularization, Pathologic; D009447:Neuroblastoma / Q000098:blood supply* / Q000235:genetics*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D020917:Receptor, trkA / Q000235:genetics*; D020813:Receptor, trkB / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D020917:Receptor, trkA; D020813:Receptor, trkB