Netrin-1 acts as a survival factor for aggressive neuroblastoma.

Céline Delloye-Bourgeois (1) , Julien Fitamant (1) , Andrea Paradisi (1) , David Cappellen (2) , Setha Douc-Rasy (2) , Marie-Anne Raquin (3) , Dwayne Stupack (4) , Akira Nakagawara (5) , Raphaël Rousseau (6) , Valérie Combaret (7) , Alain Puisieux (8) , Dominique Valteau-Couanet (3) , Jean Bénard (9, 2) , Agnès Bernet (1) , Patrick Mehlen (1, 10)

1 Apoptose Cancer et Développement
2 IMC (UMR 8126) - Interactions moléculaires et cancer
3 Département de Pédiatrie
4 departement of Pathology
5 Division od Biochemistry
6 Département de Pédiatrie
7 Laboratoire d'Oncologie Moléculaire
8 equipe 2
9 Département de biologie et pathologie médicales [Gustave Roussy]
10 Apoptosis, Cancer, and Development Laboratory

Neuroblastoma (NB), the most frequent solid tumor of early childhood, is diagnosed as a disseminated disease in >60% of cases, and several lines of evidence support the resistance to apoptosis as a prerequisite for NB progression. We show that autocrine production of netrin-1, a multifunctional laminin-related molecule, conveys a selective advantage in tumor growth and dissemination in aggressive NB, as it blocks the proapoptotic activity of the UNC5H netrin-1 dependence receptors. We show that such netrin-1 up-regulation is a potential marker for poor prognosis in stage 4S and, more generally, in NB stage 4 diagnosed infants. Moreover, we propose that interference with the netrin-1 autocrine loop in malignant neuroblasts could represent an alternative therapeutic strategy, as disruption of this loop triggers in vitro NB cell death and inhibits NB metastasis in avian and mouse models.

Domaines: Biologie moléculaire

Céline Delloye-Bourgeois, Julien Fitamant, Andrea Paradisi, David Cappellen, Setha Douc-Rasy, et al.. Netrin-1 acts as a survival factor for aggressive neuroblastoma.. Journal of Experimental Medicine, 2009, 206 (4), pp.833-47. ⟨10.1084/jem.20082299⟩. ⟨hal-00475533⟩