作者: Monica Hecht , Maria Papoutsi , Hoa Dinh Tran , Joerg Wilting , Lothar Schweigerer
DOI: 10.1158/0008-5472.CAN-04-1014
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摘要: Neuroblastoma is the most frequent solid childhood malignancy. Despite aggressive therapy, mortality high due to rapid tumor progression advanced stages. The molecules and mechanisms underlying poor prognosis are not well understood. Here, we report that cultured human neuroblastoma cells express hepatocyte growth factor (HGF) its receptor c-Met. Binding of HGF c-Met triggers autophosphorylation, indicating functional relevance this interaction. activates several downstream effectors such as mitogen-activated protein kinases extracellular signal-regulated kinase 1/extracellular 2 phospholipase C-gamma, whereas signal transducer activator transcription 3 constitutively activated in expressing In addition, able stimulate expression proteolytic activity matrix metalloproteinase-2 tissue-type plasminogen cells, thereby promoting degradation components. We show stimulates invasion vitro vivo, it promotes formation angiogenic neuroblastomas vivo. These processes can be blocked by specific inhibitors cascade, also a dominant negative mutant. Our data provide first evidence HGF/c-Met pathway essential for invasiveness malignant neuroblastomas. They further suggest may suitable therapeutic agents improve clinical outcome