title: Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas.
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.
authors.affiliation: 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.
authors.forename: Laura
authors.initials: L
authors.lastname: Broutier
authors.affiliation: 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.
authors.forename: Marion
authors.initials: M
authors.lastname: Creveaux
authors.affiliation: 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.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Vial
authors.affiliation: 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.
authors.forename: Antonin
authors.initials: A
authors.lastname: Tortereau
authors.affiliation: 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.
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Delcros
authors.affiliation: 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.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Chazot
authors.affiliation: TGF-beta and immune evasion - Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286 Centre Léon Bérard, Lyon, France.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: McCarron
authors.affiliation: Service Anatomie et Cytologie pathologiques du Centre Léon Bérard, Lyon, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Léon
authors.affiliation: INSERM UMR U917 Université Rennes 1 EFS Bretagne Equipe Labellisée Ligue Contre le Cancer, Rennes, France CHU de Rennes Pôle Biologie, Rennes, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Pangault
authors.affiliation: ANIPATH Université de Lyon, Lyon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gadot
authors.affiliation: Service Anatomie et Cytologie pathologiques du Centre Léon Bérard, Lyon, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Colombe
authors.affiliation: CHU de Rennes Pôle Biologie, Rennes, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Boulland
authors.affiliation: 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.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Blachier
authors.affiliation: TGF-beta and immune evasion - Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286 Centre Léon Bérard, Lyon, France.
authors.forename: Julien C
authors.initials: JC
authors.lastname: Marie
authors.affiliation: Service d'Anatomopathologie, Université de Lyon Hospices Civils de Lyon, Lyon, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Traverse-Glehen
authors.affiliation: Adipogen, Epalinges, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Donzé
authors.affiliation: Service Anatomie et Cytologie pathologiques du Centre Léon Bérard, Lyon, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Chassagne-Clément
authors.affiliation: Pathology of lymphoid cells Université de Lyon Service d'Hématologie, Lyon, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.affiliation: INSERM UMR U917 Université Rennes 1 EFS Bretagne Equipe Labellisée Ligue Contre le Cancer, Rennes, France CHU de Rennes Pôle Biologie, Rennes, France.
authors.forename: Karin
authors.initials: K
authors.lastname: Tarte
authors.affiliation: 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.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mehlen
authors.affiliation: 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.
authors.forename: Marie
authors.initials: M
authors.lastname: Castets
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D045744:Cell Line, Tumor; D000075389:DCC Receptor; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology* / Q000628:therapy*; D020522:Lymphoma, Mantle-Cell / Q000473:pathology* / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors*; D000075388:Netrin-1; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D000075389:DCC Receptor; C501909:DCC protein, human; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1
keywords: DCC; apoptosis; dependence receptors; netrin‐1; non‐Hodgkin lymphoma