The combination of gamma-interferon and tumor necrosis factor causes a rapid and extensive differentiation of human neuroblastoma cells.
Cancer Res
; 52(4): 931-9, 1992 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-1371090
ABSTRACT
Neuroblastoma (NB), a tumor originating from the sympathetic nervous system, is the most common extracranial neurological tumor of childhood. Human NB cells may differentiate in vitro under treatment with biological agents, as gamma-interferon (IFN-gamma) and tumor necrosis factor (TNF). Unfortunately, NB cell lines resistant to the differentiation-inducing effects of both drugs have been observed. Here we demonstrate that a combination of IFN-gamma plus TNF causes extensive and generalized differentiation of NB cells toward a neuronal phenotype. Both IFN-gamma and TNF, given alone, moderately reduced cell growth and induced partial morphological maturation. Their combination further reduced cell proliferation. The combined treatment gave a synergistic rather than additive cytostatic effect, documented also by a dramatically enhanced differentiation toward a neuronal morphology. Membrane immunofluorescence showed a homologous and heterologous up-regulation of IFN-gamma receptor, as well as a marked induction of HLA Class I antigens and, to a lesser extent, of Class II antigens on NB cells induced to differentiate. Treatment of NB cell lines with IFN-gamma/TNF results in the induction of a differentiated phenotype, as indicated by the increased expression of the Mr 160,000 and 200,000 neurofilament proteins and that of microtubule-associated proteins. Evaluation of biochemical markers of neuronal differentiation confirmed the ability of the combined treatment to induce neuroblast maturation. These results suggest that the combination of IFN-gamma and TNF should be considered for experimental clinical trials in neuroblastoma.
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Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Interferon gama
/
Fator de Necrose Tumoral alfa
/
Neuroblastoma
Tipo de estudo:
Etiology_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
1992
Tipo de documento:
Article