Journal Article

Establishment and characterization of a novel treatment‐related neuroendocrine prostate cancer cell line KUCaP13

Mizuno, Kei, Okasho, Kosuke, Lin, Yen‐Yi, Collins, Colin C., Sumiyoshi, Takayuki, Inoue, Takahiro, Kobayashi, Takashi, Li, Xin, Kamiyama, Yuki, Fukui, Tomohiro, Kimura, Hiroko, Akamatsu, Shusuke, Goto, Takayuki, Wang, Yuzhuo, Ogawa, Osamu, Sunada, Takuro, Lin, Dong

2021

Overview

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. In this study, we report the establishment of a novel patient‐derived xenograft model of t‐NEPC and the successful establishment of the KUCaP13 cell line. The cell line can be maintained permanently in vitro under regular cell culture conditions and is amenable to gene engineering. The cell line should be a valuable tool for research to identify novel therapeutic targets of NEPC and to develop effective therapeutic agents.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Adenocarcinoma / Adenocarcinoma - pathology / Analysis / Androgen receptors / Androgens / Animals / Antigens / Apoptosis Regulatory Proteins - genetics / Biopsy / Cancer / Cancer therapies / Carcinoma, Neuroendocrine - genetics / Carcinoma, Neuroendocrine - pathology / Carcinoma, Neuroendocrine - secondary / Care and treatment / Cell culture / cell line / Cell Line, Tumor - metabolism / Cell Line, Tumor - pathology / Chemotherapy / Chromosomes / cultured tumor cells / Developmental plasticity / DNA Helicases - genetics / DNA-Binding Proteins - genetics / Drug Screening Assays, Antitumor / Drug therapy / Enhancer of Zeste Homolog 2 Protein - antagonists & inhibitors / Fibroblasts / Gene Deletion / Gene Expression / Genes / Genes, Neoplasm / Genes, p53 / Genes, Retinoblastoma / Genes, Tumor Suppressor / Genetic Engineering / Genetically modified organisms / Genomes / Health aspects / Heterografts / Heterozygosity / Homozygote / Humans / Karyotyping / Loss of Heterozygosity / Male / Metastasis / Mice / Mice, SCID / Middle Aged / Morphology / Neoplasm Recurrence, Local - pathology / Neoplasm Transplantation / neuroendocrine tumor / Original / p53 Protein / Patients / Penile Neoplasms - genetics / Penile Neoplasms - secondary / Penis / Prostate cancer / Prostatic Neoplasms - genetics / Prostatic Neoplasms - pathology / PTEN Phosphohydrolase - genetics / PTEN protein / Radiation therapy / Receptors, Androgen / Reversion / RNA-Binding Proteins - genetics / Transcriptomics / Tumor proteins / Tumors / xenograft