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

Victor Laurent, Adrien Guérard, Catherine Mazerolles, Sophie Le Gonidec, Aurélie Toulet, Laurence Nieto, Falek Zaidi, Bilal Majed, David Garandeau, Youri Socrier, Muriel Golzio, Thomas Cadoudal, Karima Chaoui, Cedric Dray, Bernard Monsarrat, Odile Schiltz, Yuan Yuan Wang, Bettina Couderc, Philippe Valet, Bernard Malavaud and Catherine Muller ()
Additional contact information
Victor Laurent: Université de Toulouse, UPS
Adrien Guérard: Université de Toulouse, UPS
Catherine Mazerolles: Institut Universitaire du Cancer
Sophie Le Gonidec: Université de Toulouse, UPS
Aurélie Toulet: Université de Toulouse, UPS
Laurence Nieto: Université de Toulouse, UPS
Falek Zaidi: Institut Universitaire du Cancer
Bilal Majed: Centre Hospitalier de la Région de Saint-Omer (CHRSO), Route de Blendecques
David Garandeau: Université de Toulouse, UPS
Youri Socrier: Institut Universitaire du Cancer
Muriel Golzio: Université de Toulouse, UPS
Thomas Cadoudal: Université de Toulouse, UPS
Karima Chaoui: Université de Toulouse, UPS
Cedric Dray: Université de Toulouse, UPS
Bernard Monsarrat: Université de Toulouse, UPS
Odile Schiltz: Université de Toulouse, UPS
Yuan Yuan Wang: Université de Toulouse, UPS
Bettina Couderc: Université de Toulouse, UPS
Philippe Valet: Université de Toulouse, UPS
Bernard Malavaud: Université de Toulouse, UPS
Catherine Muller: Université de Toulouse, UPS

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10230

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