Neurotrophins and neuronal versus glial differentiation in medulloblastomas and other pediatric brain tumors

被引:34
作者
Tajima, Y
Molina, RP
Rorke, LB
Kaplan, DR
Radeke, M
Feinstein, SC
Lee, VMY
Trojanowski, JQ
机构
[1] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[2] Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA
[3] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada
[4] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA
[5] Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA
关键词
pediatric brain tumor; primitive neuroectodermal tumor; Trk receptor; neurotrophin; cell differentiation;
D O I
10.1007/s004010050806
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Medulloblastomas are highly malignant and poorly understood childhood neoplasms. To determine if neurotrophins might influence the phenotypic properties of medulloblastoma in a paracrine or autocrine manner, 51 pediatric brain tumors including 20 biopsy specimens of these primitive neuroectodermal tumors (PNETs) and 31 other pediatric brain tumors were studied. Immunohistochemistry was used with antibodies to nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and NT-3, their cognate high affinity receptors as well as to neuronal and glial markers. TrkA, TrkB, and TrkC were observed in 5 (25%), 8 (40%), and 17 (85%), respectively, of these medulloblastomas while NGF, BDNF, and NT-3 were observed in 6 (30%), 8 (40%), and 3 (15%), respectively, and antibodies to neurofilament (NF) and glial fibrillary acidic proteins (GFAP) stained 16 (80%) and 11 (55%), respectively. TrkA and NGF were not observed in the same biopsy samples, while TrkB and BDNF were codistributed in 6 of the cases, all of which expressed NF proteins. TrkC and NT-3 were co-distributed in 3 of the medulloblastomas, and these areas overlapped with NF protein-positive tumor cells in all 3 cases. In contrast to medulloblastomas, TrkA and NGF co-distributed in other pediatric brain tumors, and both Trk receptors and their neurotrophins co-distributed with GFAP-positive tumor cells in 13 (42%) of the non-PNET pediatric brain tumors. The absence of medulloblastomas that contain NGF and TrkA is consistent with in vitro data demonstrating that NGF-mediated TrkA signaling induces apoptosis. Finally, this study also suggests that BDNF and NT-3 may act in a paracrine or autocrine manner through TrkB and TrkC receptors, respectively, to induce neuronal differentiation in medulloblastomas.
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页码:325 / 332
页数:8
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