Format

Send to

Choose Destination
Prostate. 2018 Dec;78(16):1262-1282. doi: 10.1002/pros.23701. Epub 2018 Aug 2.

Movember GAP1 PDX project: An international collection of serially transplantable prostate cancer patient-derived xenograft (PDX) models.

Author information

1
MD Anderson Cancer Center, Houston, Texas.
2
Erasmus Medical Center, Rotterdam, The Netherlands.
3
University of Washington, Seattle, Washington.
4
Queensland University of Technology and Australian Prostate Cancer Research Centre-Queensland, Brisbane City, Australia.
5
Vancouver Prostate Cancer Centre, Department of Urological Sciences, UBC, Vancouver, Canada.
6
Johns Hopkins University, Baltimore, Maryland.
7
Innsbruck Medical University, Innsbruck, Austria.
8
Leiden University Medical Center, Leiden, The Netherlands.
9
University Hospital Basel, Basel, Switzerland.
10
University Hospital Bern Inselspital, Bern, Switzerland.
11
University of York, York, UK.
12
Movember Foundation, Melbourne, Australia.
13
Monash University, Melbourne, Australia.

Abstract

BACKGROUND:

While it has been challenging to establish prostate cancer patient-derived xenografts (PDXs), with a take rate of 10-40% and long latency time, multiple groups throughout the world have developed methods for the successful establishment of serially transplantable human prostate cancer PDXs using a variety of immune deficient mice. In 2014, the Movember Foundation launched a Global Action Plan 1 (GAP1) project to support an international collaborative prostate cancer PDX program involving eleven groups. Between these Movember consortium members, a total of 98 authenticated human prostate cancer PDXs were available for characterization. Eighty three of these were derived directly from patient material, and 15 were derived as variants of patient-derived material via serial passage in androgen deprived hosts. A major goal of the Movember GAP1 PDX project was to provide the prostate cancer research community with a summary of both the basic characteristics of the 98 available authenticated serially transplantable human prostate cancer PDX models and the appropriate contact information for collaborations. Herein, we report a summary of these PDX models.

METHODS:

PDX models were established in immunocompromised mice via subcutaneous or subrenal-capsule implantation. Dual-label species (ie, human vs mouse) specific centromere and telomere Fluorescence In Situ Hybridization (FISH) and immuno-histochemical (IHC) staining of tissue microarrays (TMAs) containing replicates of the PDX models were used for characterization of expression of a number of phenotypic markers important for prostate cancer including AR (assessed by IHC and FISH), Ki67, vimentin, RB1, P-Akt, chromogranin A (CgA), p53, ERG, PTEN, PSMA, and epithelial cytokeratins.

RESULTS:

Within this series of PDX models, the full spectrum of clinical disease stages is represented, including androgen-sensitive and castration-resistant primary and metastatic prostate adenocarcinomas as well as prostate carcinomas with neuroendocrine differentiation. The annotated clinical characteristics of these PDXs were correlated with their marker expression profile.

CONCLUSION:

Our results demonstrate the clinical relevance of this series of PDXs as a platform for both basic science studies and therapeutic discovery/drug development. The present report provides the prostate cancer community with a summary of the basic characteristics and a contact information for collaborations using these models.

KEYWORDS:

PDX; patient-derived xenograft; prostate cancer

PMID:
30073676
DOI:
10.1002/pros.23701

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center