ArticleBritish journal of cancer2015
Anti-apoptotic role and clinical relevance of neurotrophins in diffuse large B-cell lymphomas.
Article in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Neuro-related gene signatures predict prognosis in diffuse large B-Cell lymphoma and uncover TRPV2-mediated tumor microenvironment regulation.Annals of hematology · 2026Article
- Nerve Growth Factor and Autoimmune Diseases.Current issues in molecular biology · 2023Review
- The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies.Biomolecules · 2021Review
- CD20 expression, TrkB activation and functional activity of diffuse large B cell lymphoma-derived small extracellular vesicles.British journal of cancer · 2021Article
- KDM6A promotes imatinib resistance through YY1-mediated transcriptional upregulation of TRKA independently of its demethylase activity in chronic myelogenous leukemia.Theranostics · 2021Article
- Identification of a Novel Serum Proteomic Signature for Primary Sjögren's Syndrome.Frontiers in immunology · 2021Article
- Key Markers and Epigenetic Modifications of Dental-Derived Mesenchymal Stromal Cells.Stem cells international · 2021Review
- miRNA signature associated with R-CHOP refractoriness in patients diagnosed with diffuse large B cell lymphoma.Non-coding RNA research · 2020Article
- Prohibitin (PHB) expression is associated with aggressiveness in DLBCL and flavagline-mediated inhibition of cytoplasmic PHB functions induces anti-tumor effects.Journal of experimental & clinical cancer research : CR · 2019Article
- NOX2-Dependent Reactive Oxygen Species Regulate Formyl-Peptide Receptor 1-Mediated TrkA Transactivation in SH-SY5Y Cells.Oxidative medicine and cellular longevity · 2019Article
- Dual inhibition of BDNF/TrkB and autophagy: a promising therapeutic approach for colorectal cancer.Journal of cellular and molecular medicine · 2017Article
- Low brain-derived neurotrophic factor levels are associated with active disease and poor prognosis in childhood acute leukemia.Cancer biomarkers : section A of Disease markers · 2016Article
- TrkB-containing exosomes promote the transfer of glioblastoma aggressiveness to YKL-40-inactivated glioblastoma cells.Oncotarget · 2016Article
- Nerve growth factor: role in growth, differentiation and controlling cancer cell development.Journal of experimental & clinical cancer research : CR · 2016Review
- p75 neurotrophin receptor and pro-BDNF promote cell survival and migration in clear cell renal cell carcinoma.Oncotarget · 2016Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiffuse large B-cell lymphoma (DLBCL) is a fatal malignancy that needs to identify new targets for additional therapeutic options. This study aimed to clarify the clinical and biological significance of endogenous neurotrophin (nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)) in DLBCL biopsy samples and cell lines.
methodsWe analysed expression of NGF, BDNF, and their receptors (Trk, p75(NTR)) in 51 biopsies and cell lines by immunohistochemistry, immunofluorescence, and western blotting. To investigate the biological role of BDNF/TrkB/p75(NTR) axis, effects of neurotrophin signalling inhibition were determined on tumour cell survival and vascular endothelial growth factor (VEGF) secretion. The pharmacological pan-Trk inhibitor K252a was used for in vitro and in vivo studies.
resultsA BDNF/TrkB axis was expressed in all biopsies, which was independent of the germinal centre B-cell (GCB)/non-GCB profile. p75(NTR), TrkB, and BDNF tumour scores were significantly correlated and high NGF expression was significantly associated with MUM1/IRF4, and the non-GCB subtype. Diffuse large B-cell lymphoma cell lines co-expressed neurotrophins and their receptors. The full-length TrkB receptor was found in all cell lines, which was also phosphorylated at Tyr-817. p75(NTR) was associated to Trk and not to its cell death co-receptor sortilin. In vitro, inhibition of neurotrophin signalling induced cell apoptosis. K252a caused cell apoptosis, decreased VEGF secretion, and potentiated rituximab effect, notably in less rituximab-sensitive cells. In vivo, K252a significantly reduced tumour growth and potentiated the effects of rituximab in a GCB-DLBCL xenograft model.
conclusionsThis work argues for a pro-survival role of endogenous neurotrophins in DLBCLs and inhibition of Trk signalling might be a potential treatment strategy for rituximab resistant subgroups.
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