|Budget Amount *help
¥6,200,000 (Direct Cost : ¥6,200,000)
Fiscal Year 1996 : ¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1995 : ¥3,900,000 (Direct Cost : ¥3,900,000)
Primitive neuroectodermal tumor (PNET) of the Central Nervous System are poorly understood childhood neoplasms, and medulloblastomas are the most common pediatric PNETs. Neoplastic Cells in medulloblastomas and other PNETs resemble progenitor cells of the developing central nervous system, but they also may exhibit the molecular phenotype of immature neurons or glia.
As neurotrophins play a role in regulating differentiation, proliferation, and cell death in the normal developing central nervous system, and recent evidence suggests that neurotrophins may influence the behavior of medulloblastomas, we studied 29 PNET biopsy samples (27 of which were posterior fossa medulloblastomas) by immunohistochemisty using antibodies specific for each of the major high affinity neurotrophin receptor proteins, ie, TrkA,and TrkC.A subset of these tumors also was examined by Western blot. Immunoreactive TrkA,TrkB,and TrkC were observed in neoplastic cells in 20%, 50% of these PNETs, respectively. TrkA and TrkB were mainly observed in follicular structures, and TrkC was observed in undifferentiated tumor cells, not in follicular structures. Additional immunohistochemical studies of a subset of these PNETs using antibodies to neurotrophins that primarily activate TrkB and TrkC,ie, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5, showed that immunoreactive brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 were detected in 20,10, and 20% of these PNET biopsies, respectively.
The demonstration here that neurotrophins and their cognate receptor proteins are expressed in PNETs may immply that signal transduction pathways mediated by neurotrophins and/or their receptors influence the induction or progression of these common childhood neoplasms.
Trk Cが未分化な腫瘍細胞で発現し、Trk A, Trk Bが神経細胞への分化度の高い腫瘍細胞で発現する傾向のあることは、PNETの病態における神経成長因子の関与を示唆すると同時に、細胞内チロシンキナーゼドメインを有するひとつないし複数のリセプターが、シグナル伝達系を介してPNETの細胞増殖や細胞分化に深く関与する可能性を示唆するものと思われた.