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EMBO Mol Med. 2016 Feb 1;8(2):96-104. doi: 10.15252/emmm.201505480.

Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas.

Author information

1
Dependence Receptors, Cancer and Development Laboratory - Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286 Université de Lyon Centre Léon Bérard, Lyon, France.
2
Dependence Receptors, Cancer and Development Laboratory - Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286 Université de Lyon Centre Léon Bérard, Lyon, France Ecole Nationale Vétérinaire de Lyon, Lyon, France.
3
TGF-beta and immune evasion - Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286 Centre Léon Bérard, Lyon, France.
4
Service Anatomie et Cytologie pathologiques du Centre Léon Bérard, Lyon, France.
5
INSERM UMR U917 Université Rennes 1 EFS Bretagne Equipe Labellisée Ligue Contre le Cancer, Rennes, France CHU de Rennes Pôle Biologie, Rennes, France.
6
ANIPATH Université de Lyon, Lyon, France.
7
CHU de Rennes Pôle Biologie, Rennes, France.
8
Service d'Anatomopathologie, Université de Lyon Hospices Civils de Lyon, Lyon, France.
9
Adipogen, Epalinges, Switzerland.
10
Pathology of lymphoid cells Université de Lyon Service d'Hématologie, Lyon, France.
11
Dependence Receptors, Cancer and Development Laboratory - Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286 Université de Lyon Centre Léon Bérard, Lyon, France patrick.mehlen@lyon.unicancer.fr marie.castets@lyon.unicancer.fr.

Abstract

DCC (Deleted in Colorectal Carcinoma) has been demonstrated to constrain tumor progression by inducing apoptosis unless engaged by its ligand netrin-1. This has been shown in breast and colorectal cancers; however, this tumor suppressive function in other cancers is not established. Using a transgenic mouse model, we report here that inhibition of DCC-induced apoptosis is associated with lymphomagenesis. In human diffuse large B-cell lymphoma (DLBCL), an imbalance of the netrin-1/DCC ratio suggests a loss of DCC-induced apoptosis, either via a decrease in DCC expression in germinal center subtype or by up-regulation of netrin-1 in activated B-cell (ABC) one. Such imbalance is also observed in mantle cell lymphoma (MCL). Using a netrin-1 interfering antibody, we demonstrate both in vitro and in vivo that netrin-1 acts as a survival factor for ABC-DLBCL and MCL tumor cells. Together, these data suggest that interference with the netrin-1/DCC interaction could represent a promising therapeutic strategy in netrin-1-positive DLBCL and MCL.

KEYWORDS:

DCC; apoptosis; dependence receptors; netrin‐1; non‐Hodgkin lymphoma

PMID:
26882243
PMCID:
PMC4734837
DOI:
10.15252/emmm.201505480
[Indexed for MEDLINE]
Free PMC Article

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