Adipocytes promote prostate cancer stem cell self-renewal through amplification of the cholecystokinin autocrine loop

Tang, Kai-Dun, Liu, Ji, Jovanovic, Lidija, An, Jiyuan, Hill, Michelle M., Vela, Ian, Lee, Terence Kin-Wah, Ma, Stephanie, Nelson, Colleen, Russell, Pamela J., Clements, Judith A. and Ling, Ming-Tat (2015) Adipocytes promote prostate cancer stem cell self-renewal through amplification of the cholecystokinin autocrine loop. Oncotarget, 7 4: 4939-4948. doi:10.18632/oncotarget.6643

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Author Tang, Kai-Dun
Liu, Ji
Jovanovic, Lidija
An, Jiyuan
Hill, Michelle M.
Vela, Ian
Lee, Terence Kin-Wah
Ma, Stephanie
Nelson, Colleen
Russell, Pamela J.
Clements, Judith A.
Ling, Ming-Tat
Title Adipocytes promote prostate cancer stem cell self-renewal through amplification of the cholecystokinin autocrine loop
Journal name Oncotarget   Check publisher's open access policy
ISSN 1949-2553
Publication date 2015-12-17
Year available 2016
Sub-type Article (original research)
DOI 10.18632/oncotarget.6643
Open Access Status File (Publisher version)
Volume 7
Issue 4
Start page 4939
End page 4948
Total pages 10
Place of publication Albany, NY, United States
Publisher Impact Journals
Language eng
Subject 2730 Oncology
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.
Keyword Adipocytes
Cholecystokinin
Prostate tumor-initiating cells
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID APP1031221
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
UQ Diamantina Institute Publications
 
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