Anti-apoptotic role and clinical relevance of neurotrophins in diffuse large B-cell lymphomas - Université de Limoges Accéder directement au contenu
Article Dans Une Revue British Journal of Cancer Année : 2015

Anti-apoptotic role and clinical relevance of neurotrophins in diffuse large B-cell lymphomas

Barbara Petit
  • Fonction : Auteur
  • PersonId : 756413
  • IdRef : 15780996X
Fabrice Lalloué
Anne-Laure Fauchais
  • Fonction : Auteur
  • PersonId : 862208


Background: Diffuse 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. Methods: We analysed expression of NGF, BDNF, and their receptors (Trk, p75NTR) in 51 biopsies and cell lines by immunohistochemistry, immunofluorescence, and western blotting. To investigate the biological role of BDNF/TrkB/p75NTR 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. Results: A BDNF/TrkB axis was expressed in all biopsies, which was independent of the germinal centre B-cell (GCB)/non-GCB profile. p75NTR, 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. p75NTR 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. Conclusions: This 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.


Fichier principal
Vignette du fichier
bjc2015274a.pdf (1.66 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-01500853 , version 1 (03-04-2017)



Lydie Dubanet, Hafidha Bentayeb, Barbara Petit, Agnès Olivrie, Sofiane Saada, et al.. Anti-apoptotic role and clinical relevance of neurotrophins in diffuse large B-cell lymphomas. British Journal of Cancer, 2015, 113 (6), pp.934-944. ⟨10.1038/bjc.2015.274⟩. ⟨hal-01500853⟩
122 Consultations
139 Téléchargements



Gmail Facebook Twitter LinkedIn More