Progenitors from the central nervous system drive neurogenesis in cancer
Authors: Yves Allory
Virginie Firlej
Philippe Mauffrey
Alexis-Pierre Bemelmans
Claire Magnon
Vilma Barroca
Paul-Henri Rom√©o
Nicolas Tchitchek
Journal: Nature (2019)
Discipline: Multidisciplinary
Keywords: Autonomic nerve fibres; tumour microenvironment; cancer initiation; dissemination; neural progenitors
Affiliations: UMR967 (Laboratoire Cancer et Microenvironnement ATIP/AVENIR-INSERM-CEA), Institut de Radiobiologie Cellulaire et Mol√©culaire, Institut de Biologie Fran√ßois Jacob, Direction de la Recherche Fondamentale, Paris, France., UMR1184 (INSERM-CEA-Universit√© Paris Saclay), Infectious Diseases Models for Innovative Therapies, Institut de Biologie Fran√ßois Jacob, Direction de la Recherche Fondamentale, Paris, France., UMR9199 (CNRS-CEA-Universit√© Paris-Saclay), Molecular Imaging Research CENter, Institut de Biologie Fran√ßois Jacob, Direction de la Recherche Fondamentale, Paris, France., U955 (INSERM), H√¥pital Henri Mondor-Universit√© Paris-Est, Paris, France., Department of Pathology, Institut Curie, Paris, France., UMR967 (INSERM-CEA-Universit√© Paris Diderot-Universit√© Paris Saclay), Laboratoire R√©paration et Transcription dans les Cellules Souches, Institut de Radiobiologie Cellulaire et Mol√©culaire, Institut de Biologie Fran√ßois Jacob, Direction de la Recherche Fondamentale, Paris, France., UMR967 (Laboratoire Cancer et Microenvironnement ATIP/AVENIR-INSERM-CEA), Institut de Radiobiologie Cellulaire et Mol√©culaire, Institut de Biologie Fran√ßois Jacob, Direction de la Recherche Fondamentale, Paris, France. .

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. 

Retracted: No

PubPeer comments:
 What is happening in the flow plots in Extended Data Fig. 6c d and 7b? It seems very strange that lots of cells fall right on the gating line, but none randomly fall on the other side. Then, in Extended Data Fig. 7b, there s a red point in the same place of both SVZ and OB in the grey gate, when it seems like the coloring is supposed to be by gate. ,