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.
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