학술논문
Targeting netrin‐1/DCC interaction in diffuse large B‐cell and mantle cell lymphomas
Document Type
article
Author
Laura Broutier; Marion Creveaux; Jonathan Vial; Antonin Tortereau; Jean‐Guy Delcros; Guillaume Chazot; Mark J McCarron; Sophie Léon; Céline Pangault; Nicolas Gadot; Amélie Colombe; Marie‐Laure Boulland; Jonathan Blachier; Julien C Marie; Alexandra Traverse‐Glehen; Olivier Donzé; Catherine Chassagne‐Clément; Gilles Salles; Karin Tarte; Patrick Mehlen; Marie Castets
Source
EMBO Molecular Medicine, Vol 8, Iss 2, Pp 96-104 (2016)
Subject
Language
English
ISSN
1757-4684
1757-4676
1757-4676
Abstract
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.