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Review
. 2019 Jan 20;8(1):74.
doi: 10.3390/cells8010074.

Application of Prostate Cancer Models for Preclinical Study: Advantages and Limitations of Cell Lines, Patient-Derived Xenografts, and Three-Dimensional Culture of Patient-Derived Cells

Takeshi Namekawa  1   2 , Kazuhiro Ikeda  3 , Kuniko Horie-Inoue  4 , Satoshi Inoue  5   6
Affiliations
Review

Application of Prostate Cancer Models for Preclinical Study: Advantages and Limitations of Cell Lines, Patient-Derived Xenografts, and Three-Dimensional Culture of Patient-Derived Cells

Takeshi Namekawa et al. Cells. .

Abstract

Various preclinical models have been developed to clarify the pathophysiology of prostate cancer (PCa). Traditional PCa cell lines from clinical metastatic lesions, as exemplified by DU-145, PC-3, and LNCaP cells, are useful tools to define mechanisms underlying tumorigenesis and drug resistance. Cell line-based experiments, however, have limitations for preclinical studies because those cells are basically adapted to 2-dimensional monolayer culture conditions, in which the majority of primary PCa cells cannot survive. Recent tissue engineering enables generation of PCa patient-derived xenografts (PDXs) from both primary and metastatic lesions. Compared with fresh PCa tissue transplantation in athymic mice, co-injection of PCa tissues with extracellular matrix in highly immunodeficient mice has remarkably improved the success rate of PDX generation. PDX models have advantages to appropriately recapitulate the molecular diversity, cellular heterogeneity, and histology of original patient tumors. In contrast to PDX models, patient-derived organoid and spheroid PCa models in 3-dimensional culture are more feasible tools for in vitro studies for retaining the characteristics of patient tumors. In this article, we review PCa preclinical model cell lines and their sublines, PDXs, and patient-derived organoid and spheroid models. These PCa models will be applied to the development of new strategies for cancer precision medicine.

Keywords: cell line; organoid; patient-derived xenograft; prostate cancer; spheroid.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Application of prostate cancer models for preclinical study derived from fresh patient specimens. Each platform has its own advantages and limitations in terms of study design and expected outcome. Traditional cell lines are usually established from metastatic lesions and basically adapted to 2-dimensional monolayer culture. In contrast to cell line platform, recently developed platforms of patient-derived xenograft (PDX) and patient-derived cancer cells (PDCs) in 3-dimensional organoids/spheroids have advantages, as they often retain the characteristics of the original tumor including tumor heterogeneity and complexity. PDX models have advantages, including microenvironment, but limitations due to immunodeficient host background. PDCs can be also applied to PDX models with improved success rates for tumor formation or secondary PDC organoids/spheroids can be regenerated from PDX models vice versa. Organoid/spheroid culture and xenograft models derived from PCa cell lines can also be generated, although these platforms have limitations as they are apart from the actual behavior of clinical prostate cancer without original clinical data.
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