Establishment of primary patient-derived xenografts of palliative TURP specimens to study castrate-resistant prostate cancer

Mitchell G Lawrence, David W Pook, Hong Wang, Laura H Porter, Mark Frydenberg, John Kourambas, Sree Appu, Christine Poole, Emma Kate Beardsley, Andrew J Ryan, Sam Norden, Melissa Papargiris, Gail P Risbridger, Renea A Taylor

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Abstract

BACKGROUND: Fresh patient specimens of castrate-resistant prostate cancer (CRPC) are invaluable for studying tumor heterogeneity and responses to current treatments. They can be used for primary patient-derived xenografts (PDXs) or serially transplantable PDXs, but only a small proportion of samples grow successfully. To improve the efficiency and quality of PDXs, we investigated the factors that determine the initial engraftment of patient tissues derived from TURP specimens. METHODS: Fresh tissue was collected from castrate patients who required a TURP for urinary symptoms. Tissue was grafted under the renal capsule of immune-compromised mice for up to 14 weeks. The abundance of cancer in ungrafted and grafted specimens was compared using histopathology. Mice were castrated or implanted with testosterone pellets to determine the androgen-responsiveness of CRPC PDXs from TURP tissue. RESULTS: Primary PDXs were successfully established from 7 of 10 patients that underwent grafting. Of the 112 grafts generated from these 10 patients, 21 contained cancer at harvest. Grafts were most successful when the original patient specimens contained high amounts of viable cancer, defined as samples with (i) at least 50 cancer cells, (ii) no physical damage, and (iii) detectable Ki67 expression. PDX grafts survived in castrated hosts and proliferated in response to testosterone, confirming that they were castrate resistant but androgen-responsive. CONCLUSIONS: Primary PDXs of CRPC can be established from TURP specimens with modest success. The take rate can be increased if the original tissues contain sufficient numbers of actively proliferating cancer cells. Selecting specimens with abundant viable cancer will maximize the rate of engraftment and increase the efficiency of establishing PDXs that can be serially transplanted. Prostate 9999: XX-XX, 2015. (c) 2015 Wiley Periodicals, Inc.
Original languageEnglish
Pages (from-to)1475 - 1483
Number of pages9
JournalProstate
Volume75
Issue number13
DOIs
Publication statusPublished - 2015

Cite this

@article{8af8bad20f9746a4826efa5c42804e6d,
title = "Establishment of primary patient-derived xenografts of palliative TURP specimens to study castrate-resistant prostate cancer",
abstract = "BACKGROUND: Fresh patient specimens of castrate-resistant prostate cancer (CRPC) are invaluable for studying tumor heterogeneity and responses to current treatments. They can be used for primary patient-derived xenografts (PDXs) or serially transplantable PDXs, but only a small proportion of samples grow successfully. To improve the efficiency and quality of PDXs, we investigated the factors that determine the initial engraftment of patient tissues derived from TURP specimens. METHODS: Fresh tissue was collected from castrate patients who required a TURP for urinary symptoms. Tissue was grafted under the renal capsule of immune-compromised mice for up to 14 weeks. The abundance of cancer in ungrafted and grafted specimens was compared using histopathology. Mice were castrated or implanted with testosterone pellets to determine the androgen-responsiveness of CRPC PDXs from TURP tissue. RESULTS: Primary PDXs were successfully established from 7 of 10 patients that underwent grafting. Of the 112 grafts generated from these 10 patients, 21 contained cancer at harvest. Grafts were most successful when the original patient specimens contained high amounts of viable cancer, defined as samples with (i) at least 50 cancer cells, (ii) no physical damage, and (iii) detectable Ki67 expression. PDX grafts survived in castrated hosts and proliferated in response to testosterone, confirming that they were castrate resistant but androgen-responsive. CONCLUSIONS: Primary PDXs of CRPC can be established from TURP specimens with modest success. The take rate can be increased if the original tissues contain sufficient numbers of actively proliferating cancer cells. Selecting specimens with abundant viable cancer will maximize the rate of engraftment and increase the efficiency of establishing PDXs that can be serially transplanted. Prostate 9999: XX-XX, 2015. (c) 2015 Wiley Periodicals, Inc.",
author = "Lawrence, {Mitchell G} and Pook, {David W} and Hong Wang and Porter, {Laura H} and Mark Frydenberg and John Kourambas and Sree Appu and Christine Poole and Beardsley, {Emma Kate} and Ryan, {Andrew J} and Sam Norden and Melissa Papargiris and Risbridger, {Gail P} and Taylor, {Renea A}",
year = "2015",
doi = "10.1002/pros.23039",
language = "English",
volume = "75",
pages = "1475 -- 1483",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Blackwell",
number = "13",

}

Establishment of primary patient-derived xenografts of palliative TURP specimens to study castrate-resistant prostate cancer. / Lawrence, Mitchell G; Pook, David W; Wang, Hong; Porter, Laura H; Frydenberg, Mark; Kourambas, John; Appu, Sree; Poole, Christine; Beardsley, Emma Kate; Ryan, Andrew J; Norden, Sam; Papargiris, Melissa; Risbridger, Gail P; Taylor, Renea A.

In: Prostate, Vol. 75, No. 13, 2015, p. 1475 - 1483.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Establishment of primary patient-derived xenografts of palliative TURP specimens to study castrate-resistant prostate cancer

AU - Lawrence, Mitchell G

AU - Pook, David W

AU - Wang, Hong

AU - Porter, Laura H

AU - Frydenberg, Mark

AU - Kourambas, John

AU - Appu, Sree

AU - Poole, Christine

AU - Beardsley, Emma Kate

AU - Ryan, Andrew J

AU - Norden, Sam

AU - Papargiris, Melissa

AU - Risbridger, Gail P

AU - Taylor, Renea A

PY - 2015

Y1 - 2015

N2 - BACKGROUND: Fresh patient specimens of castrate-resistant prostate cancer (CRPC) are invaluable for studying tumor heterogeneity and responses to current treatments. They can be used for primary patient-derived xenografts (PDXs) or serially transplantable PDXs, but only a small proportion of samples grow successfully. To improve the efficiency and quality of PDXs, we investigated the factors that determine the initial engraftment of patient tissues derived from TURP specimens. METHODS: Fresh tissue was collected from castrate patients who required a TURP for urinary symptoms. Tissue was grafted under the renal capsule of immune-compromised mice for up to 14 weeks. The abundance of cancer in ungrafted and grafted specimens was compared using histopathology. Mice were castrated or implanted with testosterone pellets to determine the androgen-responsiveness of CRPC PDXs from TURP tissue. RESULTS: Primary PDXs were successfully established from 7 of 10 patients that underwent grafting. Of the 112 grafts generated from these 10 patients, 21 contained cancer at harvest. Grafts were most successful when the original patient specimens contained high amounts of viable cancer, defined as samples with (i) at least 50 cancer cells, (ii) no physical damage, and (iii) detectable Ki67 expression. PDX grafts survived in castrated hosts and proliferated in response to testosterone, confirming that they were castrate resistant but androgen-responsive. CONCLUSIONS: Primary PDXs of CRPC can be established from TURP specimens with modest success. The take rate can be increased if the original tissues contain sufficient numbers of actively proliferating cancer cells. Selecting specimens with abundant viable cancer will maximize the rate of engraftment and increase the efficiency of establishing PDXs that can be serially transplanted. Prostate 9999: XX-XX, 2015. (c) 2015 Wiley Periodicals, Inc.

AB - BACKGROUND: Fresh patient specimens of castrate-resistant prostate cancer (CRPC) are invaluable for studying tumor heterogeneity and responses to current treatments. They can be used for primary patient-derived xenografts (PDXs) or serially transplantable PDXs, but only a small proportion of samples grow successfully. To improve the efficiency and quality of PDXs, we investigated the factors that determine the initial engraftment of patient tissues derived from TURP specimens. METHODS: Fresh tissue was collected from castrate patients who required a TURP for urinary symptoms. Tissue was grafted under the renal capsule of immune-compromised mice for up to 14 weeks. The abundance of cancer in ungrafted and grafted specimens was compared using histopathology. Mice were castrated or implanted with testosterone pellets to determine the androgen-responsiveness of CRPC PDXs from TURP tissue. RESULTS: Primary PDXs were successfully established from 7 of 10 patients that underwent grafting. Of the 112 grafts generated from these 10 patients, 21 contained cancer at harvest. Grafts were most successful when the original patient specimens contained high amounts of viable cancer, defined as samples with (i) at least 50 cancer cells, (ii) no physical damage, and (iii) detectable Ki67 expression. PDX grafts survived in castrated hosts and proliferated in response to testosterone, confirming that they were castrate resistant but androgen-responsive. CONCLUSIONS: Primary PDXs of CRPC can be established from TURP specimens with modest success. The take rate can be increased if the original tissues contain sufficient numbers of actively proliferating cancer cells. Selecting specimens with abundant viable cancer will maximize the rate of engraftment and increase the efficiency of establishing PDXs that can be serially transplanted. Prostate 9999: XX-XX, 2015. (c) 2015 Wiley Periodicals, Inc.

UR - http://onlinelibrary.wiley.com/doi/10.1002/pros.23039/epdf

U2 - 10.1002/pros.23039

DO - 10.1002/pros.23039

M3 - Article

VL - 75

SP - 1475

EP - 1483

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 13

ER -