Sublethal irradiation promotes invasiveness of neuroblastoma cells

Neuroblastoma is the most frequent extracranial solid tumour of childhood. Despite multiple clinical efforts, clinical outcome has remained poor. Neuroblastoma is considered to be radiosensitive, but some clinical studies including the German trial NB90 failed to show a clinical benefit of radiation...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2005-05, Vol.330 (3), p.982-988
Main Authors: Schweigerer, Lothar, Rave-Fränk, Margret, Schmidberger, Heinz, Hecht, Monica
Format: Article
Language:English
Subjects:
c-Met
Cell Line, Tumor
Collagen
Drug Combinations
Enzyme Activation - radiation effects
Extracellular matrix
Gene Expression Regulation, Neoplastic - radiation effects
GROWTH FACTORS
Hepatocyte Growth Factor - metabolism
HGF
Humans
IN VITRO
Invasion
Irradiation
Laminin
Matrix Metalloproteinases - genetics
Matrix Metalloproteinases - metabolism
METASTASES
Mitogens - metabolism
Neoplasm Invasiveness
Neuroblastoma
Neuroblastoma - pathology
Neuroblastoma - radiotherapy
Phosphorylation - radiation effects
Proteoglycans
Proto-Oncogene Proteins c-met - metabolism
RADIATION DOSES
RADIOLOGY AND NUCLEAR MEDICINE
RADIOTHERAPY
RECEPTORS
SUBLETHAL IRRADIATION
Treatment Failure
X-Rays
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Summary:Neuroblastoma is the most frequent extracranial solid tumour of childhood. Despite multiple clinical efforts, clinical outcome has remained poor. Neuroblastoma is considered to be radiosensitive, but some clinical studies including the German trial NB90 failed to show a clinical benefit of radiation therapy. The mechanisms underlying this apparent discrepancy are still unclear. We have therefore investigated the effects of radiation on neuroblastoma cell behaviour in vitro. We show that sublethal doses of irradiation up-regulated the expression of the hepatocyte growth factor (HGF) and its receptor c-Met in some neuroblastoma cell lines. The increase in HGF/c-Met expression was correlated with enhanced invasiveness and activation of proteases degrading the extracellular matrix. Thus, irradiation at sublethal doses may promote the metastatic dissemination of neuroblastoma cells through activating the HGF/c-Met pathway and triggering matrix degradation.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2005.03.068