Open AccessEstablishment and characterization of a novel treatment‐related neuroendocrine prostate cancer cell line KUCaP13
Author(s) -
Okasho Kosuke,
Mizuno Kei,
Fukui Tomohiro,
Lin YenYi,
Kamiyama Yuki,
Sunada Takuro,
Li Xin,
Kimura Hiroko,
Sumiyoshi Takayuki,
Goto Takayuki,
Kobayashi Takashi,
Lin Dong,
Wang Yuzhuo,
Collins Colin C.,
Inoue Takahiro,
Ogawa Osamu,
Akamatsu Shusuke
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14935
Subject(s) - cancer research , cell culture , prostate cancer , biology , gene knockdown , ezh2 , cancer , epigenetics , gene , genetics
The prevalence of neuroendocrine prostate cancer (NEPC) arising from adenocarcinoma (AC) upon potent androgen receptor (AR) pathway inhibition is increasing. Deeper understanding of NEPC biology and development of novel therapeutic agents are needed. However, research is hindered by the paucity of research models, especially cell lines developed from NEPC patients. We established a novel NEPC cell line, KUCaP13, from tissue of a patient initially diagnosed with AC which later recurred as NEPC. The cell line has been maintained permanently in vitro under regular cell culture conditions and is amenable to gene engineering with lentivirus. KUCaP13 cells lack the expression of AR and overexpress NEPC‐associated genes, including SOX2, EZH2, AURKA, PEG10, POU3F2, ENO2 , and FOXA2 . Importantly, the cell line maintains the homozygous deletion of CHD1 , which was confirmed in the primary AC of the index patient. Loss of heterozygosity of TP53 and PTEN , and an allelic loss of RB1 with a transcriptomic signature compatible with Rb pathway aberration were revealed. Knockdown of PEG10 using shRNA significantly suppressed growth in vivo. Introduction of luciferase allowed serial monitoring of cells implanted orthotopically or in the renal subcapsule. Although H3K27me was reduced by EZH2 inhibition, reversion to AC was not observed. KUCaP13 is the first patient‐derived, treatment‐related NEPC cell line with triple loss of tumor suppressors critical for NEPC development through lineage plasticity. It could be valuable in research to deepen the understanding of NEPC.