Metastatic phenotype in CWR22 prostate cancer xenograft following castration

CWR22 is a human xenograft model of primary prostate cancer (PCa) that is often utilized to study castration recurrent (CR) PCa. CWR22 recapitulates clinical response to androgen deprivation therapy (ADT), in that tumors regress in response to castration, but can recur after a period of time.

Two cohorts of mice, totaling 117 mice were implanted with CWR22, allowed to develop tumors, castrated by pellet removal and followed for a period of 32 and 50 weeks. Mice presenting with tumors >2. 0 cm(3) at the primary site, moribund appearance, or palpable masses other than the primary tumor were sacrificed prior to the endpoint of the study. Tumor tissue, serum, and abnormal lesions were collected upon necropsy and analyzed by IHC, H&E, and PCR for presence of metastatic lesions arising from CWR22.

Herein, we report that CWR22 progresses after castration from a primary, hormonal therapy-naïve tumor to metastatic disease in 20% of castrated nude mice. Histological examination of CWR22 primary tumors revealed distinct pathologies that correlated with metastatic outcome after castration.

This is the first report and characterization of spontaneous metastasis in the CWR22 model, thus, CWR22 is a bona-fide model of clinical PCa representing the full progression from androgen-sensitive, primary PCa to metastatic CR-PCa. Prostate 9999: XX-XX, 2015. © 2015 Wiley Periodicals, Inc.

The Prostate. 2015 Dec 08 [Epub ahead of print]

Steven J Seedhouse, Hayley C Affronti, Ellen Karasik, Bryan M Gillard, Gissou Azabdaftari, Dominic J Smiraglia, Barbara A Foster

Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York. , Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York. , Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York. , Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York. , Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York. , Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York. , Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York.

PubMed