Characterisation of cell lines derived from prostate cancer patients with localised disease

Abstract

Background Prostate cancer is a broad-spectrum disease, spanning from indolent to a highly aggressive lethal malignancy. Prostate cancer cell lines are essential tools to understanding the basic features of this malignancy, as well as in identifying novel therapeutic strategies. However, most cell lines routinely used in prostate cancer research are derived from metastatic disease and may not fully elucidate the molecular events underlying the early stages of cancer development and progression. Thus, there is a need for new cell lines derived from localised disease to better span the disease spectrum. Methods Prostatic tissue from the primary site, and adjacent non-cancerous tissue was obtained from four patients with localised disease undergoing radical prostatectomy. Epithelial cell outgrowths were immortalised with human papillomavirus type 16 (HPV16) E6 and E7 to establish monoclonal cell lines. Chromosomal ploidy was imaged and STR profiles were determined. Cell morphology, colony formation and cell proliferation characteristics were assessed. Androgen receptor (AR) expression and AR-responsiveness to androgen treatment were analysed by immunofluorescence and RT-qPCR, respectively. RNA-seq analysis was performed to identify prostate lineage markers and expression of prostate cancer tumorigenesis-related genes. Results Two benign cell lines derived from non-cancer cells (AQ0420 and AQ0396) and two tumour tissue derived cancer cell lines (AQ0411 and AQ0415) were immortalised from four patients with localised prostatic adenocarcinoma. The cell lines presented an epithelial morphology and a slow to moderate proliferative rate. None of the cell lines formed anchorage independent colonies or displayed AR-responsiveness. Comparative RNA-seq expression analysis confirmed the prostatic lineage of the four cell lines, with a distinct gene expression profile from that of the metastatic prostate cancer cell lines, PC-3 and LNCaP. Conclusions Comprehensive characterization of these cell lines may provide new in vitro tools that could bridge the current knowledge gap between benign, early-stage and metastatic disease.

An orthotopic prostate cancer model for new treatment development using syngeneic or patient‐derived tumors

“…The common prostate cancer models use immortalized cell lines or preserved and passaged tumor biopsies from patients with prostate cancer growing subcutaneously in immune deficient mice. [5][6][7][8][9] These subcutaneous tumors may be less representative of human cancer, in part because of the ectopic host tumor microenvironment. [14][15][16] This study describes a novel technique for establishing an orthotopic prostate cancer mouse model suitable for either syngeneic or patient-derived tumors and monitoring tumor progression over time or in response to treatment using MR imaging.…”

“…In contrast, the patient derived NEPC model may be more representative of the genetic and molecular state of highgrade human prostate cancer but requires a host with impaired adaptive immunity. Of note, our orthotopic implantation and MR monitoring approach potentially is applicable to a wide range of prostate cell line, PDX, or syngeneic tumors, [5][6][7][8][9]12 the choice of which will depend on the specific molecular, genetic, or microenvironmental features of greatest interest in a particular study.…”

“…However, prostate cancer research has been limited by a lack of relevant preclinical models that mirror the clinical setting. The common prostate cancer models use immortalized cell lines or preserved and passaged tumor biopsies from patients with prostate cancer growing subcutaneously in immune deficient mice 5–9 . These subcutaneous tumors may be less representative of human cancer, in part because of the ectopic host tumor microenvironment 14–16 …”

“…A common approach has been to use human tumor cell lines or tissues implanted subcutaneously in recipient immunocompromised mice. A variety of tumor models based on immortalized cell lines or preserved and passaged tumor biopsies from patients with prostate cancer have been described 5–9 . A major limitation is the requirement for an immunosuppressed host system, which limits the ability to study the immune microenvironment and immunotherapy.…”

Identifying drug sensitivity of multifocal primary prostate cancer

“…Such exploration of direct drug-mediated biologic responses in PCa, has been hampered by the slow progression of the disease and lack of suitable cell models, depicted by the limited number of PCa cell lines available, especially for primary stage, AR+ and treatment-naive PCa 16,17 , with the exception of 22Rv1 or E006AA 18,19 . This limitation can be circumvented using patient-derived organoids (PDOs), which have the potential to recapitulate cell type composition and tumour-specific molecular features.…”