@article{7006f95697fd418a88837055866e0847,
title = "Establishing a cryopreservation protocol for patient-derived xenografts of prostate cancer",
abstract = "Background: Serially transplantable patient-derived xenografts (PDXs) are invaluable preclinical models for studying tumor biology and evaluating therapeutic agents. As these models are challenging to establish from prostate cancer specimens, the ability to preserve them through cryopreservation has several advantages for ongoing research. Despite this, there is still uncertainty about the ability to cryopreserve PDXs of prostate cancer. This study compared three different cryopreservation protocols to identify a method that can be used to reproducibly cryopreserve a diverse cohort of prostate cancer PDX models. Methods: One serially transplantable prostate cancer PDX from the Melbourne Urological Research Alliance cohort was used to compare three cryopreservation protocols: slow freezing in fetal calf serum (FCS) with 10% dimethyl sulfoxide (DMSO), FCS with 10% DMSO supplemented with the Rho-associated kinase (ROCK) inhibitor Y-27632 and vitrification. The efficiency of the slow freezing protocols was then assessed in 17 additional prostate cancer PDXs. Following cryopreservation, PDXs were re-established in host mice that were either intact and supplemented with testosterone or castrated. Graft take rate, tumor growth, histological features, and transcriptome profiles before and after cryopreservation were compared. Results: Slow freezing maintained the viability and histological features of prostate cancer PDXs, and the addition of a ROCK inhibitor increased their growth following cryopreservation. Using the slow freezing method, we re-established 100% of PDXs grown in either testosterone-supplemented or castrated host mice. Importantly, the long-term tumor growth rate and transcriptome profile were maintained following cryopreservation. Conclusion: This study has identified a protocol to reliably cryopreserve and re-establish a diverse cohort of serially transplantable PDXs of prostate cancer. This study has the potential to significantly improve the practicality of maintaining PDX models. Cryopreservation may also increase the accessibility of these important resources and provide new opportunities for preclinical studies on a broader spectrum of prostate tumors.",
keywords = "castration-resistant prostate cancer, freezing, localized prostate cancer, patient-derived xenografts",
author = "Porter, {Laura H.} and Lawrence, {Mitchell G.} and Hong Wang and Clark, {Ashlee K.} and Andrew Bakshi and Daisuke Obinata and David Goode and Melissa Papargiris and Mural and David Clouston and Andrew Ryan and Sam Norden and Eva Corey and Nelson, {Peter S.} and Isaacs, {John T.} and Jeremy Grummet and John Kourambas and Shahneen Sandhu and Murphy, {Declan G.} and David Pook and Mark Frydenberg and Taylor, {Renea A.} and Risbridger, {Gail P.}",
note = "Funding Information: We thank the patients and families who generously supported this research by consenting to provide tissue. We thank Wallace Crellin for invaluable advice, the Australian Prostate Cancer BioResource for specimen collection, the Melbourne Urological Research Alliance for providing PDXs and the Monash Histology Platform for technical assistance. This study was supported by the US Department of Defense, through the Prostate Cancer Research Program under Award No. W81XWH1810347, W81XWH1810348, and W81XWH1810349. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. This study was also supported by funding from the National Health and Medical Research Council (Project Grants 1059855, 1077799, 1138242, 1140222, and 1156570; Fellowship to Gail P. Risbridger 1002648), the Victorian Government through the Victorian Cancer Agency (Fellowships to Renea A. Taylor MCRF15023 and Mitchell G. Lawrence MCRF18017; CAPTIV program), the Endocrine Society of Australia (Research Seed Grant to Mitchell G. Lawrence), Monash University Faculty of Medicine, Nursing and Health Sciences (Bridging Post‐doctoral Fellowship to Laura H. Porter), the EJ Whitten Foundation, the Peter and Lyndy White Foundation, and TissuPath Pathology. The financial support for establishing new PDXs was provided by the Movember Foundation, as a project of the Global Action Plan 1 (GAP1) PDX project. Funding Information: Endocrine Society of Australia, Grant/Award Number: Research Seed Grant; Victorian Cancer Agency, Grant/Award Numbers: MCRF15023, MCRF18017, CAPTIV; Faculty of Medicine, Nursing and Health Sciences, Monash University, Grant/Award Number: Bridging Post‐doctoral Fellowship; Peter and Lyndy White Foundation; EJ Whitten Foundation; TissuPath Pathology; Movember Foundation, Grant/Award Number: Global Action Plan 1; Congressionally Directed Medical Research Programs, Grant/Award Numbers: W81XWH1810348, W81XWH1810349, W81XWH1810347; National Health and Medical Research Council, Grant/Award Numbers: 1059855, 1138242, 1156570, 1002648, 1077799, 1140222 Publisher Copyright: {\textcopyright} 2019 Wiley Periodicals, Inc.",
year = "2019",
month = aug,
day = "1",
doi = "10.1002/pros.23839",
language = "English (US)",
volume = "79",
pages = "1326--1337",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "11",
}