Targeting netrin-3 in small cell lung cancer and neuroblastoma.

Autor: Jiang S; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut PLAsCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France., Richaud M; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut PLAsCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France., Vieugué P; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut PLAsCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France., Rama N; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut PLAsCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France., Delcros JG; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut PLAsCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France.; Small Molecules for Biological Targets, Centre de Recherche en Cancérologie de Lyon, UMR INSERM 1052 - CNRS 5286 ISPB Rockefeller, Lyon, France., Siouda M; Univ Lyon, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Lyon, France., Sanada M; Toray Industries, Inc., New Frontiers Research Labs, Kanagawa, Japan., Redavid AR; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut PLAsCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France., Ducarouge B; Netris Pharma, Lyon, France., Hervieu M; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut PLAsCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France., Breusa S; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut PLAsCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France., Manceau A; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut PLAsCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France., Gattolliat CH; CNRS UMR 8126, University Paris-Sud 11, Institut Gustave Roussy, Villejuif, France., Gadot N; Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, Lyon, France., Combaret V; Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, Lyon, France., Neves D; Netris Pharma, Lyon, France., Ortiz-Cuaran S; Univ Lyon, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Lyon, France., Saintigny P; Univ Lyon, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Lyon, France., Meurette O; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut PLAsCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France., Walter T; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut PLAsCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France.; Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Gastroentérologie et d'Oncologie Digestive, Lyon Cedex 03, France., Janoueix-Lerosey I; INSERM, U830, Génétique et Biologie des Cancers, Institut Curie, Paris, France., Hofman P; Laboratory of Clinical and Experimental Pathology, Université Côte d'Azur, CHU Nice, FHU OncoAge, Pasteur Hospital, Nice, France., Mulligan P; Univ Lyon, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Lyon, France., Goldshneider D; Netris Pharma, Lyon, France., Mehlen P; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut PLAsCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France.; Univ Lyon, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Lyon, France., Gibert B; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut PLAsCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France.; Univ Lyon, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Lyon, France.
Jazyk: angličtina
Zdroj: EMBO molecular medicine [EMBO Mol Med] 2021 Apr 09; Vol. 13 (4), pp. e12878. Date of Electronic Publication: 2021 Mar 15.
DOI: 10.15252/emmm.202012878
Abstrakt: The navigation cue netrin-1 is well-documented for its key role in cancer development and represents a promising therapeutic target currently under clinical investigation. Phase 1 and 2 clinical trials are ongoing with NP137, a humanized monoclonal antibody against netrin-1. Interestingly, the epitope recognized by NP137 in netrin-1 shares 90% homology with its counterpart in netrin-3, the closest member to netrin-1 in humans, for which little is known in the field of cancer. Here, we unveiled that netrin-3 appears to be expressed specifically in human neuroblastoma (NB) and small cell lung cancer (SCLC), two subtypes of neuroectodermal/neuroendocrine lineages. Netrin-3 and netrin-1 expression are mutually exclusive, and the former is driven by the MYCN oncogene in NB, and the ASCL-1 or NeuroD1 transcription factors in SCLC. Netrin-3 expression is correlated with disease stage, aggressiveness, and overall survival in NB. Mechanistically, we confirmed the high affinity of netrin-3 for netrin-1 receptors and we demonstrated that netrin-3 genetic silencing or interference using NP137, delayed tumor engraftment, and reduced tumor growth in animal models. Altogether, these data support the targeting of netrin-3 in NB and SCLC.
(© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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