Transcriptomics

Dataset Information

26

Neurogenesis in Prostate Cancer is driven by Neural Precursors from the Central Nervous System


ABSTRACT: The development of autonomic nerve fibres in the tumour microenvironment is a pivotal event that regulates prostate cancer initiation and dissemination, but how nerves emerge in tumours is presently unknown. Here we show that Doublecortine-expressing (DCX+) neural precursors from the central nervous system (CNS) infiltrate prostate tumours and differentiate into neo-neurons that contribute to tumour development. In human primary prostate tumours and transgenic mouse cancer tissues, the density of DCX+ neural progenitors is strongly associated with tumour aggressiveness, invasion and recurrence. We found that DCX+ neural precursors egress from the subventricular zone, a neurogenic area of the CNS, and circulate in the blood to reach the tumour where they initiate neurogenesis. Hence, the DCX+ cells in prostate tumour can differentiate into neurons ex vivo and build up a tumour-associated neural network in vivo. Selective genetic depletion of DCX+ cells in mice significantly inhibits the early phases of prostate cancer development, whereas orthotopic transplantation of DCX+ cells purified from prostate tumour or brain tissues promotes tumour growth and cancer cell dissemination. These results unveil a unique crosstalk between the CNS and the tumour that drives a process of neurogenesis necessary for prostate cancer development, and indicate a novel neural element of the tumour microenvironment as a potential target for cancer treatment.

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Mus musculus  

SUBMITTER: Claire Magnon   Nicolas Tchitchek  

PROVIDER: E-MTAB-7727 | ArrayExpress | 2019-05-16

SECONDARY ACCESSION(S): ERP114116

REPOSITORIES: ArrayExpress, ENA

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Publications

Progenitors from the central nervous system drive neurogenesis in cancer.

Mauffrey Philippe P   Tchitchek Nicolas N   Barroca Vilma V   Bemelmans Alexis-Pierre AP   Firlej Virginie V   Allory Yves Y   Roméo Paul-Henri PH   Magnon Claire C  

Nature 20190515 7758


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 associa  ...[more]

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