Neurotrophins and neuronal versus glial differentiation in medulloblastomas and other pediatric brain tumors |
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Authors: | Yasuo Tajima R P Molina Jr Lucy B Rorke David R Kaplan Monte Radeke Stuart C Feinstein Virginia M-Y Lee J Q Trojanowski |
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Institution: | (1) Department of Pathology and Laboratory Medicine, University of Pennsylvania, 3601 Spruce Street, HUP/3rd Floor Maloney, Philadelphia, PA 19104-4283, USA Tel.: 1-215-662-6920; Fax: 1-215-349-5909; e-mail: trojanow@mail.med.upenn.edu, US;(2) Department of Pathology and Laboratory Medicine, University of Pennsylvania and Department of Pathology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA, US;(3) Montreal Neurological Institute, Montreal, Quebec, Canada, CA;(4) Department of Molecular, Cellular, and Development Biology and Neuroscience Research Institute, University of California, Santa Barbara, CA, USA, US |
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Abstract: | 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 co-distributed 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.
Received: 2 October 1997 / Revised, accepted: 29 December 1997 |
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Keywords: | Pediatric brain tumor Primitive neuroectodermal tumpor Trk receptor Neurotrophin Cell differentiation |
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