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

Kai Dun Tang, Ji Liu, Lidija Jovanovic, Jiyuan An, Michelle M. Hill, Ian Vela, Kin Wah Lee, Stephanie Ma, Colleen Nelson, Pamela J. Russell, Judith A. Clements, Ming Tat Ling

Research output: Journal article publicationJournal articleAcademic researchpeer-review

14 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)4939-4948
Number of pages10
JournalOncotarget
Volume7
Issue number4
DOIs
Publication statusPublished - 1 Jan 2016
Externally publishedYes

Keywords

  • Adipocytes
  • Cholecystokinin
  • Prostate tumor-initiating cells

ASJC Scopus subject areas

  • Oncology

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