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 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.
Schweigerer
Lothar
L
Department of Pediatrics, University of Goettingen, Germany.
Rave-Fränk
Margret
M
Schmidberger
Heinz
H
Hecht
Monica
M
D045744:Cell Line, Tumor; D003094:Collagen; D004338:Drug Combinations; D004789:Enzyme Activation / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007797:Laminin; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008934:Mitogens / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009447:Neuroblastoma / Q000473:pathology* / Q000532:radiotherapy*; D010766:Phosphorylation / Q000528:radiation effects; D011509:Proteoglycans; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D017211:Treatment Failure; D014965:X-Rays
D004338:Drug Combinations; C066855:HGF protein, human; D007797:Laminin; D008934:Mitogens; D011509:Proteoglycans; C059485:matrigel; D017228:Hepatocyte Growth Factor; D003094:Collagen; D019859:Proto-Oncogene Proteins c-met; D020782:Matrix Metalloproteinases