title: Adipocytes promote prostate cancer stem cell self-renewal through amplification of the cholecystokinin autocrine loop.
abstract: Obesity has long been linked with prostate cancer progression, although the underlying mechanism is still largely unknown. Here, we report that adipocytes promote the enrichment of prostate cancer stem cells (CSCs) through a vicious cycle of autocrine amplification. In the presence of adipocytes, prostate cancer cells actively secrete the peptide hormone cholecystokinin (CCK), which not only stimulates prostate CSC self-renewal, but also induces cathepsin B (CTSB) production of the adipocytes. In return, CTSB facilitates further CCK secretion by the cancer cells. More importantly, inactivation of CCK receptor not only suppresses CTSB secretion by the adipocytes, but also synergizes the inhibitory effect of CTSB inhibitor on adipocyte-promoted prostate CSC self-renewal. In summary, we have uncovered a novel mechanism underlying the mutual interplay between adipocytes and prostate CSCs, which may help explaining the role of adipocytes in prostate cancer progression and provide opportunities for effective intervention.
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland & Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Kai-Dun
authors.initials: KD
authors.lastname: Tang
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland & Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Ji
authors.initials: J
authors.lastname: Liu
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland & Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Lidija
authors.initials: L
authors.lastname: Jovanovic
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland & Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Jiyuan
authors.initials: J
authors.lastname: An
authors.affiliation: The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Hill
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland & Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Vela
authors.affiliation: Department of Pathology, Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Terence Kin-Wah
authors.initials: TK
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ma
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland & Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Colleen
authors.initials: C
authors.lastname: Nelson
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland & Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Russell
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland & Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Clements
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland & Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Ming-Tat
authors.initials: MT
authors.lastname: Ling
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019898:Autocrine Communication; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D000066673:Cell Self Renewal / Q000187:drug effects*; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000494:pharmacology*; D002853:Chromatography, Liquid; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry
chemical_list: D012333:RNA, Messenger; D002766:Cholecystokinin
keywords: adipocytes; cholecystokinin; prostate tumor-initiating cells