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In vivo angiogenic activity of neuroblastoma correlates with MYCN oncogene overexpression
Author(s) -
Ribatti Domenico,
Raffaghello Lizzia,
Pastorino Fabio,
Nico Beatrice,
Brignole Chiara,
Vacca Angelo,
Ponzoni Mirco
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10742
Subject(s) - neuroblastoma , angiogenesis , oncogene , chorioallantoic membrane , cancer research , in vivo , cell culture , biopsy , pathology , biology , embryo , cell , medicine , microbiology and biotechnology , cell cycle , genetics
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. © 2002 Wiley‐Liss, Inc.