Mitogenesis in glioblastoma multiforme cell lines: a role for NGF and its TrkA receptors.

摘要: Neurotrophins have definitive roles in the growth/maintenance of neuronal populations, but their function malignant gliomas is unknown. The ability for nerve growth factor (NGF) to serve as a mitogenic agent was investigated several human glioblastoma multiforme (GBM) cell lines, including U251, U87, and U373. In serum-free medium, addition NGF (200 ng/ml) these lines increased counts over controls, after 3 days culture by 9%, 16%, 33%, respectively. Dose-dependent increases [3H]thymidine uptake were found more rigorously U373 line. Proteins both high affinity NGF-specific tyrosine kinase binding site (p140TrkA; TrkA) low neurotrophin (p75NTR) receptor present all three GBM lines. TrkA mRNA identified (only line studied). NGF-stimulated proliferation inhibited dose-dependent fashion K252a, blocker Trk-induced kinases. NGF, measured ELISA, detectable even 7 medium. These data suggest that can be enhanced acting via Trk phosphorylation. Future studies antiproliferative therapies should consider agents directed against intracellular signaling cascades.