In vivo angiogenic activity of neuroblastoma correlates with MYCN oncogene overexpression.
Neuroblastoma (NB) is the most common malignant solid tumor in early childhood. Amplification of the MYCN oncogene is associated with a more malignant course of disease and poor outcome. The role that MYCN plays in the regulation of angiogenesis in NB remains unclear. To better elucidate this matter, fresh biopsy samples from 21 patients, 10 with MYCN-amplified tumors (defined as having >10 copies of the oncogene) and 11 with nonamplified tumors, were tested for their angiogenic capacity using the chick embryo chorioallantoic membrane assay, a useful model for such investigation. Moreover, using the same experimental model, conditioned media obtained from 5 different human NB cell lines MYCN-amplified (HTLA-230, LAN-5 and GI-LI-N) or nonamplified (ACN and SH-SY5Y) and biopsy fragments obtained from xenografts derived from 4 NB cell lines (HTLA-230, GI-LI-N, ACN and SH-SY5Y) injected in nude mice were assayed for angiogenic potential. Our results clearly demonstrated that MYCN amplification parallels angiogenesis in NB. When fresh biopsy samples from patients, CM derived from NB cell lines and biopsy fragments derived from xenografts of the same cell lines injected in nude mice were tested, the response was univocal: the angiogenic response, evaluated both macroscopically and microscopically, was significantly higher in the MYCN-amplified specimens compared to the nonamplified ones.
Ribatti
Domenico
D
Department of Human Anatomy and Histology, University of Bari, Policlinico, Bari, Italy. ribatti@anatomia.uniba.it
Raffaghello
Lizzia
L
Pastorino
Fabio
F
Nico
Beatrice
B
Brignole
Chiara
C
Vacca
Angelo
A
Ponzoni
Mirco
M
D000293:Adolescent; D000482:Allantois / Q000098:blood supply; D000818:Animals; D001706:Biopsy; D002642:Chick Embryo; D002648:Child; D002675:Child, Preschool; D002823:Chorion / Q000098:blood supply; D017077:Culture Media, Conditioned; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008833:Microcirculation; D000071447:N-Myc Proto-Oncogene Protein; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D009447:Neuroblastoma / Q000098:blood supply* / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D010524:Peripheral Nervous System Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins