Abstract:
:Aberrant epidermal growth factor receptor (EGFR) expression promotes the pathogenesis of malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy associated with neurofibromatosis type 1, but the mechanisms by which EGFR expression promotes MPNST pathogenesis are poorly understood. We hypothesized that inappropriately expressed EGFRs promote MPNST invasion and found that these kinases are concentrated in MPNST invadopodia in vitro. Epidermal growth factor receptor knockdown inhibited the migration of unstimulated MPNST cells in vitro, and exogenous EGF further enhanced MPNST migration in a substrate-specific manner, promoting migration on laminin and, to a lesser extent, collagen. In this setting, EGF acts as a chemotactic factor. We also found that the 7 known EGFR ligands (EGF, betacellulin, epiregulin, heparin-binding EGF, transforming growth factor-α [TGF-α], amphiregulin, and epigen) variably enhanced MPNST migration in a concentration-dependent manner, with TGF-α being particularly potent. With the exception of epigen, these factors similarly promoted the migration of nonneoplastic Schwann cells. Although transcripts encoding all 7 EGFR ligands were detected in human MPNST cells and tumor tissues, only TGF-α was consistently overexpressed and was found to colocalize with EGFR in situ. These data indicate that constitutive EGFR activation, potentially driven by autocrine or paracrine TGF-α signaling, promotes the aggressive invasive behavior characteristic of MPNSTs.
journal_name
J Neuropathol Exp Neuroljournal_title
Journal of neuropathology and experimental neurologyauthors
Byer SJ,Brossier NM,Peavler LT,Eckert JM,Watkins S,Roth KA,Carroll SLdoi
10.1097/NEN.0b013e3182859939subject
Has Abstractpub_date
2013-03-01 00:00:00pages
219-33issue
3eissn
0022-3069issn
1554-6578journal_volume
72pub_type
杂志文章abstract::Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an autosomal-dominant disorder involving the cerebral, retinal, renal, and other systemic microvessels due to frameshift mutations in the TREX1 gene. Under physiological conditions, the TREX1 protein is localized in the cellular cytoplasm and perinuclear area...
journal_title:Journal of neuropathology and experimental neurology
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doi:10.1093/jnen/nly115
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199903000-00008
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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doi:10.1097/01.jnen.0000171644.00180.fc
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abstract::Oligodendrogliomas are characterized by frequent loss of heterozygosity (LOH) on chromosomes 1p and 19q, but additional genetic alterations are likely to be involved. In this study, we screened 28 oligodendrogliomas (WHO grade II) and 20 anaplastic oligodendrogliomas (WHO grade III) for alterations in the RB1/CDK4/p16...
journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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doi:10.1093/jnen/61.2.186
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:
更新日期:1981-01-01 00:00:00
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198707000-00004
更新日期:1987-07-01 00:00:00
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/62.3.260
更新日期:2003-03-01 00:00:00
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199501000-00007
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abstract::Injury to neonatal nerves, unlike adult nerves, results in poor regeneration and extensive motoneuron death. We examined whether exposure to a more mature nerve environment could rescue axotomized motoneurons following neonatal injury. The sciatic nerve in 1 hindlimb of 3-day-old (P3) rats was transected and the cut e...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/62.1.75
更新日期:2003-01-01 00:00:00
abstract::β-Amyloid (Aβ) plaques can trigger chronic inflammation in the cellular environment that recruits infiltrating macrophages during the course of Alzheimer disease (AD). Activated macrophages release pro-inflammatory cytokines that increase neurotoxicity associated with AD. A major impediment to investigating neuroinfla...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlaa093
更新日期:2020-11-01 00:00:00
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199812000-00009
更新日期:1998-12-01 00:00:00
abstract::Spinal muscular atrophy (SMA) is characterized by loss of motor neurons in the spinal cord that results in muscle denervation and profound weakness in affected patients. We sought evidence for primary muscle involvement in the disease during human development by analyzing the expression of several muscle cytoskeletal ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000078
更新日期:2014-06-01 00:00:00
abstract::Cerebral palsy is a common birth disorder that frequently involves ischemic-type injury to developing white matter (WM). Dead glial cells are a common feature of this injury and here we describe a novel form of acute ischemic cell death in developing WM astrocytes. Ischemia, modeled by the withdrawal of oxygen and glu...
journal_title:Journal of neuropathology and experimental neurology
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abstract::The 2016 WHO classification of brain tumors represents a major step towards the integration of molecular data into pathologic diagnoses. Our institution has included massively parallel sequencing technology in the diagnostic work-up of all gliomas since January 2016. The utilized platform successfully identifies copy ...
journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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doi:10.1097/00005072-199203000-00006
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abstract::The tau deposits found in neurodegenerative diseases are classified based on their isoforms, that is, 3-repeat (3R) tau and 4-repeat (4R) tau. These isoforms are distinguishable using the antibodies RD3 and RD4, respectively, and Gallyas (Gal) and Campbell-Switzer (CS) silver staining methods, respectively. Tau is als...
journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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abstract::Retinoblastoma protein (pRb) is a ubiquitous 928-amino acid cell cycle regulatory molecule with diverse biologic activities. One critical function of pRb is the control of the G1-to-S phase checkpoint of the cell cycle. In the hypophosphorylated state, pRb suppresses the activity of E2F transcription factors thereby i...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3182204414
更新日期:2011-07-01 00:00:00
abstract::Clinical and neuropathological staging of Alzheimer disease (AD) neurodegeneration and neuronal loss dynamics is the baseline for identification of treatment targets and timing. The aim of this study of 14 brain regions in 25 subjects diagnosed with AD and 13 age-matched control subjects was to establish the pattern o...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlaa140
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章,评审
doi:
更新日期:1992-09-01 00:00:00
abstract::Progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), sporadic multisystem tauopathy, and some forms of frontotemporal dementia with Parkinsonism linked to chromosome 17 are characterized by neuronal and glial lesions accumulating tau protein containing 4 conserved repeats in microtubule-binding domai...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/01.jnen.0000218446.38158.61
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abstract::Large complex membranous bodies are described in the cerebral cortex of adult rats. Although these bodies are not very prevalent, they appear with increasing frequency as the age of the animal increases from 12 to 28 months. The membranous bodies are composed of varying amounts of membranes, cytoplasm and empty vacuol...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197603000-00003
更新日期:1976-03-01 00:00:00
abstract::The neurodegenerative synucleinopathies, which include Parkinson disease, multiple-system atrophy, and Lewy body disease, are characterized by the presence of abundant neuronal inclusions called Lewy bodies and Lewy neurites. These disorders remain incurable, and a greater understanding of the pathologic processes is ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000262
更新日期:2015-12-01 00:00:00
abstract::Mutation A30P in the alpha-synuclein gene is a cause of familial Parkinson disease. Transgenic mice expressing wild mouse and mutant human A30P alpha-synuclein, Tg5093 mice (Tg), show a progressive motor disorder characterized by tremor, rigidity, and dystonia, accompanied by accumulation of alpha-synuclein in the som...
journal_title:Journal of neuropathology and experimental neurology
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更新日期:2004-04-01 00:00:00
abstract::The prognosis of gliomas is generally poor since these tumors elude established therapeutic approaches. Immunotherapy might present an effective therapy in particular because the glioma cells are diffusely dispersed in the infiltration zone of the tumor and show a strong propensity to invade the surrounding brain alon...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
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abstract::Chronic experimental allergic encephalomyelitis (EAE), produced in inbred guinea pigs given a single inoculation during the juvenile period with isologous spinal cord in complete Freund's adjuvant, has been studied by light and electron microscopy. Most animals showed a delayed onset of nurologic signs from 12 to 68 w...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197505000-00001
更新日期:1975-05-01 00:00:00