title: Periprostatic adipocytes act as a driving force for prostate cancer progression in obesity.
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.
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Biologie du Cancer" et "Biologie Structurale et Biophysique", CNRS; Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31077, France.
authors.forename: Victor
authors.initials: V
authors.lastname: Laurent
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Biologie du Cancer" et "Biologie Structurale et Biophysique", CNRS; Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31077, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Guérard
authors.affiliation: Département d'Anatomo-Pathologie, Institut Universitaire du Cancer, Toulouse cedex 9 31059, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Mazerolles
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Tissu Adipeux, Obésité et Diabète", Institut National de la Santé et de la Recherche Médicale, INSERM U1048, Toulouse F-31432, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Le Gonidec
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Biologie du Cancer" et "Biologie Structurale et Biophysique", CNRS; Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31077, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Toulet
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Biologie du Cancer" et "Biologie Structurale et Biophysique", CNRS; Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31077, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Nieto
authors.affiliation: Département d'Anatomo-Pathologie, Institut Universitaire du Cancer, Toulouse cedex 9 31059, France.
authors.forename: Falek
authors.initials: F
authors.lastname: Zaidi
authors.affiliation: Centre Hospitalier de la Région de Saint-Omer (CHRSO), Route de Blendecques, BP 60357, Saint-Omer Cedex 62505, France.
authors.forename: Bilal
authors.initials: B
authors.lastname: Majed
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Biologie du Cancer" et "Biologie Structurale et Biophysique", CNRS; Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31077, France.
authors.forename: David
authors.initials: D
authors.lastname: Garandeau
authors.affiliation: Département d'Anatomo-Pathologie, Institut Universitaire du Cancer, Toulouse cedex 9 31059, France.
authors.forename: Youri
authors.initials: Y
authors.lastname: Socrier
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Biologie du Cancer" et "Biologie Structurale et Biophysique", CNRS; Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31077, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Golzio
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Tissu Adipeux, Obésité et Diabète", Institut National de la Santé et de la Recherche Médicale, INSERM U1048, Toulouse F-31432, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cadoudal
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Biologie du Cancer" et "Biologie Structurale et Biophysique", CNRS; Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31077, France.
authors.forename: Karima
authors.initials: K
authors.lastname: Chaoui
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Tissu Adipeux, Obésité et Diabète", Institut National de la Santé et de la Recherche Médicale, INSERM U1048, Toulouse F-31432, France.
authors.forename: Cedric
authors.initials: C
authors.lastname: Dray
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Biologie du Cancer" et "Biologie Structurale et Biophysique", CNRS; Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31077, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Monsarrat
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Biologie du Cancer" et "Biologie Structurale et Biophysique", CNRS; Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31077, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Schiltz
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Biologie du Cancer" et "Biologie Structurale et Biophysique", CNRS; Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31077, France.
authors.forename: Yuan Yuan
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Tumeur et Environnement", Centre de Recherche en Cancérologie de Toulouse (CRCT), Toulouse Cedex 1 F-31037, France.
authors.forename: Bettina
authors.initials: B
authors.lastname: Couderc
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Tissu Adipeux, Obésité et Diabète", Institut National de la Santé et de la Recherche Médicale, INSERM U1048, Toulouse F-31432, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département d'Urologie, Institut Universitaire du Cancer, Toulouse cedex 9 31059, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Malavaud
authors.affiliation: Université de Toulouse, UPS, Toulouse F-31077, France.|Département "Biologie du Cancer" et "Biologie Structurale et Biophysique", CNRS; Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31077, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Muller
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology; D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D054410:Chemokine CCL7 / Q000378:metabolism*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D011379:Prognosis; D011467:Prostate; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D054397:Receptors, CCR3 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D054410:Chemokine CCL7; D054397:Receptors, CCR3