Hepatocyte growth factor (HGF) and receptor (c-met) in normal and malignant astrocytic cells

Background: Hepatocyte growth factor (HGF) is a multifunctional peptide tha t binds to a specific receptor c-met. Both HGF and c-met have been identifi ed in normal brain and on glial tumors. The purpose of this study is to fur ther define the biologic importance of HGF and c-met on normal and malignan t glial cells grown in vitro. Materials and Methods: Nine human malignant g lioma-derived tumor cell cultures and cultures of astrocytes derived from n ormal brain were examined for c-met and HGF transcripts using Northern blot or RT-PCR analysis. Cellular invasiveness was quantitated by mechanical as say and mitogenesis was determined by cell count. Results: C-met was expres sed in five of seven malignant glioma-derived tumor cell cultures and in bo th normal astrocyte cultures. HGF transcript was not detected in any of the cell cultures. HGF supplementation enhanced invasiveness in c-met positive cell lines and did not alter cellular mitogenesis in the assayed cultures Conclusions: These findings suggest that HGF is a potent stimulator of inva siveness in c-met positive malignant glioma-derived tumor cells and is not an active cytokine with regards to in vitro glial cell proliferation. HGF m ay therefore stimulate glioma cellular invasion in vivo through binding to its receptor and by activating tyrosine kinase secondary messengers.