title: Induction of neuroendocrine differentiation in castration resistant prostate cancer cells by adipocyte differentiation-related protein (ADRP) delivered by exosomes.
abstract: Although overall mortality rate of prostate cancer (PCa) declines in recent years, castration-resistant prostate cancer (CRPC) remains incurable. Clinical evidence indicates that CRPC recurred from hormonal therapy exhibits neuroendocrine differentiated (NED) phenotypes, which could contribute to therapeutic resistance and poor survival. Understanding the onset of NED could lead us to develop new therapeutic strategies for CRPC. Although PCa is known as a lipid-enriched tumor, its role in CRPC development is not fully understood. In this study, we demonstrated that IL-6 or androgen deprivation therapy (ADT)-induced lipid accumulation is associated with NED phenotypes. IL-6 or ADT can induce NED in PCa cells via peroxisome proliferator-activated receptor γ (PPARγ, a major lipogenic transcription factor) and adipocyte differentiation-related protein (ADRP, a major component of adiposome). In addition, ADRP protein can be detected in exosomes released from these cells and these exosomes are capable of inducing NED of PCa cells in a paracrine fashion. Understanding the role of PPARγ/ADRP in NED could provide new target(s) for CRPC therapy.
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan; Department of Urology, University of Texas Southwestern Medical Center Dallas, TX, USA.
authors.forename: Li-Chiung
authors.initials: LC
authors.lastname: Lin
authors.affiliation: Department of Urology, University of California Davis, CA, USA.
authors.forename: Allen C
authors.initials: AC
authors.lastname: Gao
authors.affiliation: Department of Microbiology and Immunology, Molecular Infectious Disease Research Center, Chang Gung University and Chang Gung Memorial Hospital, Taoyuan, Taiwan. Electronic address: chlai@mail.cgu.edu.tw.
authors.forename: Chih-Ho
authors.initials: CH
authors.lastname: Lai
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center Dallas, TX, USA; Graduate Institute of Cancer Biology, China Medical University Hospital, Taichung, Taiwan. Electronic address: JT.Hsieh@UTSouthwestern.edu.
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan. Electronic address: hlin@dragon.nchu.edu.tw.
authors.forename: Ho
authors.initials: H
authors.lastname: Lin
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D002454:Cell Differentiation; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D008297:Male; D000070780:Perilipin-2 / Q000235:genetics* / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics* / Q000378:metabolism
chemical_list: D000070780:Perilipin-2
keywords: Adipocyte differentiation-related protein; Adiposome; Castration resistant prostate cancer; Exosomes; Neuroendocrine differentiation