EMBO molecular medicine · 2016
Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Broutier Laura, Creveaux Marion, Vial Jonathan, Tortereau Antonin, Delcros Jean-Guy, Chazot Guillaume, McCarron Mark J, Léon Sophie, Pangault Céline, Gadot Nicolas, Colombe Amélie, Boulland Marie-Laure, Blachier Jonathan, Marie Julien C, Traverse-Glehen Alexandra, Donzé Olivier, Chassagne-Clément Catherine, Salles Gilles, Tarte Karin, Mehlen Patrick, Castets Marie
Аннотация
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.