Background Methods 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... Show moreBackground Methods 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. 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 Conclusion 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. 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. Show less
Badrising, S.K.; Noort, V. van der; Eertwegh, A.J.M. van den; Hamberg, P.; Oort, I.M. van; Berg, H.P. van den; ... ; DUOS 2016
BACKGROUND. Tumour cells with a stem cell-like phenotype have recently been identified in prostate tumors and it has been suggested that this population may be responsible for the diversity of cell... Show moreBACKGROUND. Tumour cells with a stem cell-like phenotype have recently been identified in prostate tumors and it has been suggested that this population may be responsible for the diversity of cell types within tumors and also for the initiation of metastases. These cells carry a number of defined markers: they are cd133 and cd44+kve and express high levels of 0(201 integrin. In this study we have, for the first time, assessed matched primary and bone marrow biopsies from prostate cancer patients for the distribution of cells carrying these and a number of other putative stem cell markers. METHODS. Eleven matched (primary and bone metastasis) specimens from prostate cancer patients were assessed for the presence of cd133, cd44, alpha 2 beta 1 integrin, CXCR4, c-met, c(6 integrin, and nestin using immunohistochemistry and stain intensity and distribution scored. RESULTS. In the bone metastases, tumor cells staining positively for cd133 were detected at low frequency in similar to 50% of samples. Staining for nestin was confined to endothelium. Positive staining of tumor cells for the other antigens was present at variable frequency in >70% of metastases with the exception of CXCR4 which was absent from all but 2 specimens. Where positive staining of tumor cells was present in the metastasis, cells staining for each antigen were present in the matched primary with the exception of cd44 which was absent in all but 2/11 matched primary tissues. CONCLUSIONS. In established metastases no single or combination of marker expression profiles identify the established metastatic phenotype, although cd44 expression was shown to be more frequent in metastases that in primary cancers. Prostate 70: 875-882, 2010. (C) 2010 Wiley-Liss, Inc. Show less
