Schweigerer Lothar, Rave-Fränk Margret, Schmidberger Heinz, Hecht Monica
Department of Pediatrics, University of Goettingen, Germany.
Biochem Biophys Res Commun. 2005 May 13;330(3):982-8. doi: 10.1016/j.bbrc.2005.03.068.
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.
神经母细胞瘤是儿童最常见的颅外实体瘤。尽管进行了多项临床努力，但其临床预后仍然很差。神经母细胞瘤被认为对放疗敏感，但包括德国NB90试验在内的一些临床研究未能显示放疗的临床益处。这种明显差异背后的机制仍不清楚。因此，我们研究了辐射对神经母细胞瘤细胞体外行为的影响。我们发现，亚致死剂量的辐射上调了某些神经母细胞瘤细胞系中肝细胞生长因子（HGF）及其受体c-Met的表达。HGF/c-Met表达的增加与侵袭性增强和降解细胞外基质的蛋白酶激活相关。因此，亚致死剂量的辐射可能通过激活HGF/c-Met途径并引发基质降解来促进神经母细胞瘤细胞的转移扩散。
