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. 2015 Jan;28(1):21-6.
doi: 10.1293/tox.2014-0050. Epub 2014 Dec 18.

Establishment of a syngeneic orthotopic model of prostate cancer in immunocompetent rats

Shugo Suzuki  1 , Aya Naiki-Ito  2 , Toshiya Kuno  2 , Wanisa Punfa  3 , Ne Long  4 , Hiroyuki Kato  2 , Shingo Inaguma  5 , Masami Komiya  6 , Tomoyuki Shirai  7 , Satoru Takahashi  2
Affiliations

Establishment of a syngeneic orthotopic model of prostate cancer in immunocompetent rats

Shugo Suzuki et al. J Toxicol Pathol. 2015 Jan.

Erratum in

  • Errata (Printer's correction).
    [No authors listed] [No authors listed] J Toxicol Pathol. 2016 Jan;29(1):74. Epub 2016 Feb 17. J Toxicol Pathol. 2016. PMID: 26989306 Free PMC article.

Abstract

We previously established 3 cell lines (PLS10, PLS20 and PLS30) from a chemically-induced prostate carcinoma in F344 rats, and demonstrated high potential for metastasis in nude mice. In the present study, we investigated the feasibility of establishing an orthotopic model using the 3 rat prostate cancer cell lines in immunocompetent rats with the aim of resolving species-mismatch problems and defects of immune systems. The PLS10, PLS20 and PLS30 cell lines were injected into the ventral prostates of 6-week-old rats, which were then sacrificed at experimental weeks 4 and 8. Tumor mass formation was found in rats with PLS10, but not in those with PLS20 or PLS30. Additionally, metastatic carcinomas could be detected in lymph nodes and lungs of PLS10-inoculated rats. Genetic analysis demonstrated K-ras gene mutations in PLS10 and PLS20, but not in PLS30 cells. There were no mutations in p53 and KLF6. In conclusion, we established a syngeneic orthotopic model for prostate cancer in immunocompetent rats simulating human castration-resistant prostate cancer (CRPC), which should prove useful for development and validation of therapeutic agents, especially with immunotherapy.

Keywords: immunocompetent animal; orthotopic model; prostate cancer; rats.

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Figures

Fig. 1.
Fig. 1.
Macroscopic findings for PLS10 tumors in the ventral prostate of F344 rats at week 8. A large tumor mass is present in the ventral lobe (arrow) (A). Low magnification view of a prostate tumor formed in the ventral lobe at experimental week 4 (B). Tumors consisted of well differentiated (C), moderately differentiated (D) and poorly differentiated (E) components, infiltrating perineural areas (F), invading vascular (G) and lymph vessels (H), and metastasizing to lymph nodes (I) and lungs (J) at experimental week 8.
Fig. 2.
Fig. 2.
K-ras gene mutations in cell lines. Aberrant localization of bands was detected in PLS10 at exon 1 and PLS20 at exon 2 of the K-ras gene by SSCP-PCR (A). Mutations of codon 13 (GGC, Gly to CGC, Arg) in PLS10 (B) and codon 61 (CAA, Gln to CTT, Leu) in PLS20 (C) were detected by sequencing.
See this image and copyright information in PMC

References

    1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, and Forman D. Global cancer statistics. CA Cancer J Clin. 61: 69–90 2011. - PubMed
    1. Damber JE, and Aus G. Prostate cancer. Lancet. 371: 1710–1721 2008. - PubMed
    1. Matsuda T, Marugame T, Kamo K, Katanoda K, Ajiki W, Sobue T; Japan Cancer Surveillance Research Group. Cancer incidence and incidence rates in Japan in 2006: based on data from 15 population-based cancer registries in the monitoring of cancer incidence in Japan (MCIJ) project. Jpn J Clin Oncol. 42: 139–147 2012. - PubMed
    1. Shirai T, Tamano S, Kato T, Iwasaki S, Takahashi S, and Ito N. Induction of invasive carcinomas in the accessory sex organs other than the ventral prostate of rats given 3,2′-dimethyl-4-aminobiphenyl and testosterone propionate. Cancer Res. 51: 1264–1269 1991. - PubMed
    1. Nakanishi H, Takeuchi S, Kato K, Shimizu S, Kobayashi K, Tatematsu M, and Shirai T. Establishment and characterization of three androgen-independent, metastatic carcinoma cell lines from 3,2′-dimethyl-4-aminobiphenyl-induced prostatic tumors in F344 rats. Jpn J Cancer Res. 87: 1218–1226 1996. - PMC - PubMed