Evidence of chromaffin oxygen sensing in neuroblastoma.
With the aid of IGF2 and VEGF in situ hybridization; tyrosine hydroxylase, chromogranin A, and Ki67 immunohistochemistry; and TUNEL staining applied to a large series of clinical neuroblastomas and to an animal model, we show here that stroma-poor neuroblastomas show evidence of chromaffin differentiation similar to that of type 1 small intensely fluorescent (SIF) cells and that this occurs in a vascular-dependent fashion, indicating a role for local tumor hypoxia in the differentiation process.
Hedborg
F
F
Department of Genetics and Pathology, University Hospital, Uppsala, Sweden. fredrik.hedborg@genpat.uu.se
Franklin
G
G
Norrman
J
J
Grimelius
L
L
Wassberg
E
E
Hero
B
B
Schilling
F
F
Berthold
F
F
Harms
D
D
Sandstedt
B
B
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D002454:Cell Differentiation; D015687:Cell Hypoxia; D019439:Chromaffin Cells / Q000737:chemistry*; D053379:Chromogranin A; D002864:Chromogranins / Q000032:analysis; D016228:Endothelial Growth Factors / Q000032:analysis; D018305:Ganglioneuroblastoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D005729:Ganglioneuroma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008222:Lymphokines / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011923:Rats, Nude; D013564:Sympathetic Nervous System / Q000737:chemistry / Q000166:cytology / Q000196:embryology; D014183:Transplantation, Heterologous; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D015415:Biomarkers; D053379:Chromogranin A; D002864:Chromogranins; D016228:Endothelial Growth Factors; D019394:Ki-67 Antigen; D008222:Lymphokines; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D007335:Insulin-Like Growth Factor II; D014446:Tyrosine 3-Monooxygenase; D010100:Oxygen