Hepatocyte growth factor and its receptor c-Met are involved in the invasion of TrkB overexpressing human neuroblastoma cells

Neuroblastoma is the most frequent solid malignancy of childhood with advanced stage mortalities of approximately 80%. Neuroblastomas have a heterogenous biological and clinical behaviour. The mechanisms underlying good or poor prognosis are still poorly understood. However, amplification/overexpression of the oncogene N-Myc and the neurotrophin receptor TrkB are known to contribute to a highly malignant phenotype.

To define the mechanisms through which TrkB may contribute to neuroblastoma progression, we overexpressed TrkB in the neuroblastoma cell lines SH-SY5Y and SK-N-AS. The transfectants, but not the controls, showed an increased invasive capacity both, in vitro and in vivo, as demonstrated by Matrigel- and chick chorioallantoic membrane assays, respectively. The invasion of neuroblastoma cells expressing TrkB can be attributed to the co-expression of the hepatocyte growth factor (HGF) and its receptor c-Met, resulting in an autocrine loop. We suggest that overexpression of TrkB in human neuroblastomas induces a constitutive and functional autocrine HGF/c-Met signalling pathway which mediates invasion and thereby contributes to neuroblastoma progression.