title: Potential therapeutic effect of epigenetic therapy on treatment-induced neuroendocrine prostate cancer.
abstract: Although adenocarcinomas of the prostate are relatively indolent, some patients with advanced adenocarcinomas show recurrence of treatment-induced neuroendocrine prostate cancer, which is highly aggressive and lethal. Detailed biological features of treatment-induced neuroendocrine prostate cancer have not been characterized owing to limited biopsies/resections and the lack of a cellular model. In this study, we used a unique cellular model (LNCaP/NE1.8) to investigate the potential role of cancer stem cells in treatment-induced neuroendocrine prostate cancer with acquired resistance to hormonal therapy and chemotherapy. We also studied the role of cancer stem cells in enhancing invasion in treatment-induced neuroendocrine prostate cancer cells that recurred after long-term androgen-ablation treatment. Using an in vitro system mimicking clinical androgen-ablation, our results showed that the neuroendocrine-like subclone NE1.8 cells were enriched with cancer stem cells. Compared to parental prostate adenocarcinoma LNCaP cells, NE1.8 cells are more resistant to androgen deprivation therapy and chemotherapeutic agents and show increased cancer cell invasiveness. Results from this study also suggest a potential epigenetic therapeutic strategy using suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, as a chemotherapeutic agent for therapy-resistant treatment-induced neuroendocrine prostate cancer cells to minimize the risk of prostate cancer recurrence and metastasis.
authors.affiliation: School of Life Sciences, Anhui University, Hefei, China.|Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Urology, The First Affiliated Hospital of SooChow University, Suzhou, China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Yan-Jing
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Alexa
authors.initials: A
authors.lastname: Cohen
authors.affiliation: Department of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Squires
authors.affiliation: Department of Pathology, Beijing Hospital, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Anhui University, Hefei, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Jiao-Ti
authors.initials: JT
authors.lastname: Huang
mesh_terms: D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic; D006801:Humans; D008297:Male; D016609:Neoplasms, Second Primary / Q000473:pathology / Q000628:therapy*; D014411:Neoplastic Stem Cells; D018358:Neuroendocrine Tumors / Q000473:pathology / Q000628:therapy*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*