Progenitors from the central nervous system drive neurogenesis in cancer

Philippe Mauffrey, Nicolas Tchitchek, Vilma Barroca, Alexis-Pierre Bemelmans, Virginie Firlej, Yves Allory, Paul-Henri Roméo and Claire Magnon ()
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Philippe Mauffrey: UMR967 (Laboratoire Cancer et Microenvironnement ATIP/AVENIR-INSERM-CEA), Institut de Radiobiologie Cellulaire et Moléculaire, Institut de Biologie François Jacob, Direction de la Recherche Fondamentale
Nicolas Tchitchek: UMR1184 (INSERM-CEA-Université Paris Saclay), Infectious Diseases Models for Innovative Therapies, Institut de Biologie François Jacob, Direction de la Recherche Fondamentale
Vilma Barroca: UMR967 (Laboratoire Cancer et Microenvironnement ATIP/AVENIR-INSERM-CEA), Institut de Radiobiologie Cellulaire et Moléculaire, Institut de Biologie François Jacob, Direction de la Recherche Fondamentale
Alexis-Pierre Bemelmans: UMR9199 (CNRS-CEA-Université Paris-Saclay), Molecular Imaging Research CENter, Institut de Biologie François Jacob, Direction de la Recherche Fondamentale
Virginie Firlej: Hôpital Henri Mondor-Université Paris-Est
Yves Allory: Institut Curie
Paul-Henri Roméo: UMR967 (INSERM-CEA-Université Paris Diderot-Université Paris Saclay), Laboratoire Réparation et Transcription dans les Cellules Souches, Institut de Radiobiologie Cellulaire et Moléculaire, Institut de Biologie François Jacob, Direction de la Recherche Fondamentale
Claire Magnon: UMR967 (Laboratoire Cancer et Microenvironnement ATIP/AVENIR-INSERM-CEA), Institut de Radiobiologie Cellulaire et Moléculaire, Institut de Biologie François Jacob, Direction de la Recherche Fondamentale

Nature, 2019, vol. 569, issue 7758, 672-678

Abstract: Abstract Autonomic nerve fibres in the tumour microenvironment regulate cancer initiation and dissemination, but how nerves emerge in tumours is currently unknown. Here we show that neural progenitors from the central nervous system that express doublecortin (DCX+) infiltrate prostate tumours and metastases, in which they initiate neurogenesis. In mouse models of prostate cancer, oscillations of DCX+ neural progenitors in the subventricular zone—a neurogenic area of the central nervous system—are associated with disruption of the blood–brain barrier, and with the egress of DCX+ cells into the circulation. These cells then infiltrate and reside in the tumour, and can generate new adrenergic neurons. Selective genetic depletion of DCX+ cells inhibits the early phases of tumour development in our mouse models of prostate cancer, whereas transplantation of DCX+ neural progenitors promotes tumour growth and metastasis. In humans, the density of DCX+ neural progenitors is strongly associated with the aggressiveness and recurrence of prostate adenocarcinoma. These results reveal a unique crosstalk between the central nervous system and prostate tumours, and indicate neural targets for the treatment of cancer.

Date: 2019
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DOI: 10.1038/s41586-019-1219-y

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