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

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.

Nature communications. 2016 Jan 12*** epublish ***

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, Catherine Muller

Université de Toulouse, UPS, Toulouse F-31077, France. , Université de Toulouse, UPS, Toulouse F-31077, France. , Département d'Anatomo-Pathologie, Institut Universitaire du Cancer, Toulouse cedex 9 31059, France. , Université de Toulouse, UPS, Toulouse F-31077, France. , Université de Toulouse, UPS, Toulouse F-31077, France. , Université de Toulouse, UPS, Toulouse F-31077, France. , Département d'Anatomo-Pathologie, Institut Universitaire du Cancer, Toulouse cedex 9 31059, France. , Centre Hospitalier de la Région de Saint-Omer (CHRSO), Route de Blendecques, BP 60357, Saint-Omer Cedex 62505, France. , Université de Toulouse, UPS, Toulouse F-31077, France. , Département d'Anatomo-Pathologie, Institut Universitaire du Cancer, Toulouse cedex 9 31059, France. , Université de Toulouse, UPS, Toulouse F-31077, France. , Université de Toulouse, UPS, Toulouse F-31077, France. , Université de Toulouse, UPS, Toulouse F-31077, France. , Université de Toulouse, UPS, Toulouse F-31077, France. , Université de Toulouse, UPS, Toulouse F-31077, France. , Université de Toulouse, UPS, Toulouse F-31077, France. , Université de Toulouse, UPS, Toulouse F-31077, France. , Université de Toulouse, UPS, Toulouse F-31077, France. , Université de Toulouse, UPS, Toulouse F-31077, France. , Université de Toulouse, UPS, Toulouse F-31077, France. , Université de Toulouse, UPS, Toulouse F-31077, France.

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