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Nat Commun. 2016 Jan 12;7:10230. doi: 10.1038/ncomms10230.

Periprostatic adipocytes act as a driving force for prostate cancer progression in obesity.

Author information

1
Université de Toulouse, UPS, Toulouse F-31077, France.
2
Département "Biologie du Cancer" et "Biologie Structurale et Biophysique", CNRS; Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31077, France.
3
Département d'Anatomo-Pathologie, Institut Universitaire du Cancer, Toulouse cedex 9 31059, France.
4
Département "Tissu Adipeux, Obésité et Diabète", Institut National de la Santé et de la Recherche Médicale, INSERM U1048, Toulouse F-31432, France.
5
Centre Hospitalier de la Région de Saint-Omer (CHRSO), Route de Blendecques, BP 60357, Saint-Omer Cedex 62505, France.
6
Département "Tumeur et Environnement", Centre de Recherche en Cancérologie de Toulouse (CRCT), Toulouse Cedex 1 F-31037, France.
7
Département d'Urologie, Institut Universitaire du Cancer, Toulouse cedex 9 31059, France.

Abstract

Obesity favours the occurrence of locally disseminated prostate cancer in the periprostatic adipose tissue (PPAT) surrounding the prostate gland. Here we show that adipocytes from PPAT support the directed migration of prostate cancer cells and that this event is strongly promoted by obesity. This process is dependent on the secretion of the chemokine CCL7 by adipocytes, which diffuses from PPAT to the peripheral zone of the prostate, stimulating the migration of CCR3 expressing tumour cells. In obesity, higher secretion of CCL7 by adipocytes facilitates extraprostatic extension. The observed increase in migration associated with obesity is totally abrogated when the CCR3/CCL7 axis is inhibited. In human prostate cancer tumours, expression of the CCR3 receptor is associated with the occurrence of aggressive disease with extended local dissemination and a higher risk of biochemical recurrence, highlighting the potential benefit of CCR3 antagonists in the treatment of prostate cancer.

Comment in

PMID:
26756352
PMCID:
PMC4729927
DOI:
10.1038/ncomms10230
[Indexed for MEDLINE]
Free PMC Article

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