Brain Lipid Binding Protein in Axon-Schwann Cell Interactions and Peripheral Nerve Tumorigenesis

Miller, Shyra J.; Li, Hongzhen; Rizvi, Tilat A.; Huang, Yuan; Johansson, Gunnar; Bowersock, Jason; Sidani, Amer; Vitullo, John C.; Vogel, Kristine S.; Parysek, Linda M.; DeClue, Jeffrey E.; Ratner, Nancy

doi:10.1128/mcb.23.6.2213-2224.2003

Cited by 39 publications

(45 citation statements)

References 59 publications

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“…While the demonstration of progesterone receptor expression in neurofibromas is potentially relevant for tumori genesis during pregnancy (McLaughlin and Jacks, 2003), the role of fatty-acid redistribution should also be explored. FABP-7 has been shown to be upregulated in neurofibromin-deficient Schwann cells and is a receptor for DHA (Xu et al, 1996;Miller et al, 2003). Here, we demonstrate that FABP-7 expression is enhanced in human neurofibromas and MPNST cells in vitro, supporting the data of Miller et al We found, however, that tumor grafts of Nf1:p53 MPNST cell lines had variable expression of FABP-7, with aggressive cell lines losing expression in vivo.…”

Section: Discussionsupporting

confidence: 80%

“…Expression profiling in Nf1À/À Schwann cells revealed dramatic induction of brain fatty-acid binding protein (FABP-7) (Feng et al, 1994;Kurtz et al, 1994;Miller et al, 2003), a protein demonstrated to bind docosahexaenoic acid (DHA) with high affinity (Xu et al, 1996). DHA is the long-chain metabolite of the essential fatty acid linolenic acid, an omega-3 fatty acid.…”

Section: Introductionmentioning

confidence: 99%

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Differential modulation of malignant peripheral nerve sheath tumor growth by omega-3 and omega-6 fatty acids

et al. 2005

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Neurofibromatosis type 1 (NF1) is a common genetic disorder of the nervous system resulting in neurofibromas and malignant peripheral nerve sheath tumors (MPNST). In this study, we report the modulation of murine and human MPNST cell growth by the fatty acids docosahexaenoic acid (DHA) and arachidonic acid (AA). DHA demonstrated a tendency to stimulate cell growth at low doses and induce apoptosis at high doses, paralleled by the activation of ERK and caspase-3. Furthermore, high-dose DHA reversed the stimulation of MPNST cell growth by a number of growth factors suggested to have a pathogenic effect in NF1 and inhibited MPNST growth in vivo. AA was found to have a reciprocal activity in vitro, stimulating MPNST cell growth at comparable concentrations and reducing DHA activation of ERK. These findings introduce fatty acids as a possible regulator of MPNST development in NF1 patients.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Differential modulation of malignant peripheral nerve sheath tumor growth by omega-3 and omega-6 fatty acids

et al. 2005

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“…Some of these might be specific to this cellular model of NF1, but multiple abnormalities are to be expected in tumor cells. In addition to genes previously known to be deregulated in NF1, such as EGFR (DeClue et al, 2000), FABP7 (Miller et al, 2003) and elements of the RAS signaling pathway (Ingram et al, 2001), many genes that are associated with the multiple stages of tumor pathogenesis have been found to be expressed abnormally in T265 cells by this gene expression-profiling method. These include cell cycle-regulatory proteins, adhesion and ECM molecules, oncogenes, tumor suppressor genes, growth factor receptors, intracellular signaling molecules and regulators of transcription.…”

Section: Discussionmentioning

confidence: 93%

“…The FGF2 receptor might play a role in MPNST proliferation and malignancy, evidence for this comes from work indicating that neurofibrosarcoma-derived (T265) Schwann cell proliferation is increased two-fold by FGF2 in vitro (Badache and De Vries, 1998). The epidermal growth factor receptor (EGFR) has been implicated in malignancy in NF1 (DeClue et al, 2000), as have downstream targets of EGFR such as BLBP (Miller et al, 2003). We have shown significant deregulation of these components in T265 cells (Table 2).…”

Section: Growth Factor Receptorsmentioning

confidence: 84%

“…The T265 cell line is widely used for cell culture studies of Schwann cells in MPNSTs (Muja et al, 2001;Badache and De Vries, 1998;Muir et al, 2001;Miller et al, 2003;Fieber et al, 2003). This cell line has characteristics consistent with Schwann cells that have been transformed into a malignant phenotype because of the loss of neurofibromin in the auto-somaldominant condition NF1; however, many genes are thought to be regulated abnormally in NF1 and in this cell line, which makes it difficult to design properly controlled experiments for studies of NF1 in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional profiling in an MPNST-derived cell line and normal human Schwann cells

et al. 2004

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AbstractcDNA microarrays were utilized to identify abnormally expressed genes in a malignant peripheral nerve sheath tumor (MPNST)-derived cell line, T265, by comparing the mRNA abundance profiles with that of normal human Schwann cells (nhSCs). The findings characterize the molecular phenotype of this important cell-line model of MPNSTs, and elucidate the contribution of Schwann cells in MPNSTs. In total, 4608 cDNA sequences were screened and hybridizations replicated on custom cDNA microarrays. In order to verify the microarray data, a large selection of differentially expressed mRNA transcripts were subjected to semi-quantitative reverse transcription PCR (LightCycler). Western blotting was performed to investigate a selection of genes and signal transduction pathways, as a further validation of the microarray data. The data generated from multiple microarray screens, semi-quantitative RT-PCR and Western blotting are in broad agreement. This study represents a comprehensive gene-expression analysis of an MPNST-derived cell line and the first comprehensive global mRNA profile of nhSCs in culture. This study has identified ~900 genes that are expressed abnormally in the T265 cell line and detected many genes not previously reported to be expressed in nhSCs. The results provide crucial information on the T265 cells that is essential for investigation using this cell line in experimental studies in neurofibromatosis type I (NF1), and important information on normal human Schwann cells that is applicable to a wide range of studies on Schwann cells in cell culture.

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Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene

et al. 2009

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Understanding the biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumours is essential, as there is a lack of tumour biomarkers, prognostic factors and therapeutics. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells (n = 10), NF1-derived primary benign neurofibroma Schwann cells (NFSCs) (n = 22), malignant peripheral nerve sheath tumour (MPNST) cell lines (n = 13), benign neurofibromas (NF) (n = 26) and MPNST (n = 6). Dermal and plexiform NFs were indistinguishable. A prominent theme in the analysis was aberrant differentiation. NFs repressed gene programs normally active in Schwann cell precursors and immature Schwann cells. MPNST signatures strongly differed; genes up-regulated in sarcomas were significantly enriched for genes activated in neural crest cells. We validated the differential expression of 82 genes including the neural crest transcription factor SOX9 and SOX9 predicted targets. SOX9 immunoreactivity was robust in NF and MPSNT tissue sections and targeting SOX9 – strongly expressed in NF1-related tumours – caused MPNST cell death. SOX9 is a biomarker of NF and MPNST, and possibly a therapeutic target in NF1.

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Brain Lipid Binding Protein in Axon-Schwann Cell Interactions and Peripheral Nerve Tumorigenesis

Abstract: Loss of axonal contact characterizes Schwann cells in benign and

Cited by 39 publications

References 59 publications

Differential modulation of malignant peripheral nerve sheath tumor growth by omega-3 and omega-6 fatty acids

Differential modulation of malignant peripheral nerve sheath tumor growth by omega-3 and omega-6 fatty acids

Transcriptional profiling in an MPNST-derived cell line and normal human Schwann cells

Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene

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