Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas

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-Clement; Gilles Salles; Karin Tarte; Patrick Mehlen; Marie Castets

doi:10.15252/emmm.201505480

Journal articles

Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas

Laura Broutier ^{1, 2} Marion Creveaux ^{1, 2} Jonathan Vial ^{1, 2} Antonin Tortereau ^{1, 2, 3} Jean-Guy Delcros ^{1, 2} Guillaume Chazot ^{1, 2} Mark J Mccarron ¹ Sophie Léon ¹ Céline Pangault ⁴ Nicolas Gadot ⁵ Amélie Colombe ¹ Marie-Laure Boulland ⁶ Jonathan Blachier ¹ Julien C Marie ¹ Alexandra Traverse-Glehen ^{7, 8} Olivier Donzé Catherine Chassagne-Clement ⁹ Gilles Salles ¹⁰ Karin Tarte ^{11, 4} Patrick Mehlen ^{2, 1} Marie Castets ^{1, 2}

1 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon

2 LabEx DEVweCAN - Développement Cancer et Thérapies Ciblées [Lyon]

3 ICE - Interactions Cellules Environnement - UR

4 MiCa - Microenvironnement et cancer

5 Anipath

6 HITC - Service d'Hématologie, Immunologie et de Thérapie Cellulaire

7 LBMC - Laboratoire de Biologie Moléculaire de la Cellule

8 Service d'Anatomie Pathologique

9 Département d'anatomopathologie, biopathologie

10 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]

11 Service d’immunologie, de thérapie cellulaire et d’hématopoïèse

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

Keywords : Apoptosis non-Hodgkin lymphoma netrin-1 dependence receptors DCC

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Journal articles

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Life Sciences [q-bio]

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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01269905
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Submitted on : Friday, February 5, 2016 - 2:17:13 PM
Last modification on : Friday, December 10, 2021 - 4:08:10 PM

Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas

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Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas

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