Adipocytes promote prostate cancer stem cell self-renewal through amplification of the cholecystokinin autocrine loop
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Kai-Dun Tang1, Ji Liu1, Lidija Jovanovic1, Jiyuan An1, Michelle M. Hill2, Ian Vela1, Terence Kin-Wah Lee3, Stephanie Ma4, Colleen Nelson1, Pamela J. Russell1, Judith A. Clements1, Ming-Tat Ling1
1Australian Prostate Cancer Research Centre-Queensland & Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia
2The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia
3Department of Pathology, Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China
4Department of Anatomy, Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China
Ming-Tat Ling, e-mail: firstname.lastname@example.org
Keywords: cholecystokinin, adipocytes, prostate tumor-initiating cells
Received: August 09, 2015 Accepted: November 27, 2015 Published: December 17, 2015
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.
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