Open AccessTargeting netrin‐1/ DCC interaction in diffuse large B‐cell and mantle cell lymphomas
Author(s) -
Broutier Laura,
Creveaux Marion,
Vial Jonathan,
Tortereau Antonin,
Delcros JeanGuy,
Chazot Guillaume,
McCarron Mark J,
Léon Sophie,
Pangault Céline,
Gadot Nicolas,
Colombe Amélie,
Boulland MarieLaure,
Blachier Jonathan,
Marie Julien C,
TraverseGlehen Alexandra,
Donzé Olivier,
ChassagneClément Catherine,
Salles Gilles,
Tarte Karin,
Mehlen Patrick,
Castets Marie
Publication year - 2016
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201505480
Subject(s) - netrin , cancer research , deleted in colorectal cancer , mantle cell lymphoma , apoptosis , lymphoma , biology , diffuse large b cell lymphoma , in vivo , colorectal cancer , immunology , cancer , receptor , axon guidance , genetics
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 .