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

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...

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Veröffentlicht in:The Prostate 2015-09, Vol.75 (13), p.1475-1483
Hauptverfasser: Lawrence, Mitchell G., Pook, David W., Wang, Hong, Porter, Laura H., Frydenberg, Mark, Kourambas, John, Appu, Sree, Poole, Christine, Beardsley, Emma K., Ryan, Andrew, Norden, Sam, Papargiris, Melissa M., Risbridger, Gail P., Taylor, Renea A.
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container_end_page 1483
container_issue 13
container_start_page 1475
container_title The Prostate
container_volume 75
creator Lawrence, Mitchell G.
Pook, David W.
Wang, Hong
Porter, Laura H.
Frydenberg, Mark
Kourambas, John
Appu, Sree
Poole, Christine
Beardsley, Emma K.
Ryan, Andrew
Norden, Sam
Papargiris, Melissa M.
Risbridger, Gail P.
Taylor, Renea A.
description 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 75:1475–1483, 2015. © 2015 Wiley Periodicals, Inc.
doi_str_mv 10.1002/pros.23039
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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 75:1475–1483, 2015. © 2015 Wiley Periodicals, Inc.</description><identifier>ISSN: 0270-4137</identifier><identifier>EISSN: 1097-0045</identifier><identifier>DOI: 10.1002/pros.23039</identifier><identifier>PMID: 26177841</identifier><identifier>CODEN: PRSTDS</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Aged ; Aged, 80 and over ; androgen ; Animals ; castrate‐resistance ; Heterografts ; Humans ; Male ; Mice ; Neoplasm Transplantation - methods ; prostate cancer ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms - surgery ; Transplantation, Heterologous - methods ; Transurethral Resection of Prostate ; TURP ; xenograft</subject><ispartof>The Prostate, 2015-09, Vol.75 (13), p.1475-1483</ispartof><rights>2015 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpros.23039$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpros.23039$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26177841$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lawrence, Mitchell G.</creatorcontrib><creatorcontrib>Pook, David W.</creatorcontrib><creatorcontrib>Wang, Hong</creatorcontrib><creatorcontrib>Porter, Laura H.</creatorcontrib><creatorcontrib>Frydenberg, Mark</creatorcontrib><creatorcontrib>Kourambas, John</creatorcontrib><creatorcontrib>Appu, Sree</creatorcontrib><creatorcontrib>Poole, Christine</creatorcontrib><creatorcontrib>Beardsley, Emma K.</creatorcontrib><creatorcontrib>Ryan, Andrew</creatorcontrib><creatorcontrib>Norden, Sam</creatorcontrib><creatorcontrib>Papargiris, Melissa M.</creatorcontrib><creatorcontrib>Risbridger, Gail P.</creatorcontrib><creatorcontrib>Taylor, Renea A.</creatorcontrib><title>Establishment of primary patient‐derived xenografts of palliative TURP specimens to study castrate‐resistant prostate cancer</title><title>The Prostate</title><addtitle>Prostate</addtitle><description>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. 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Pook, David W. ; Wang, Hong ; Porter, Laura H. ; Frydenberg, Mark ; Kourambas, John ; Appu, Sree ; Poole, Christine ; Beardsley, Emma K. ; Ryan, Andrew ; Norden, Sam ; Papargiris, Melissa M. ; Risbridger, Gail P. ; Taylor, Renea A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p2119-a61ed27d293353fe017d5dcb9384e56d939d3c7f67bfdc9c1e64a3133f01fd993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>androgen</topic><topic>Animals</topic><topic>castrate‐resistance</topic><topic>Heterografts</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>Neoplasm Transplantation - methods</topic><topic>prostate cancer</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Prostatic Neoplasms - surgery</topic><topic>Transplantation, Heterologous - methods</topic><topic>Transurethral Resection of Prostate</topic><topic>TURP</topic><topic>xenograft</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lawrence, Mitchell G.</creatorcontrib><creatorcontrib>Pook, David W.</creatorcontrib><creatorcontrib>Wang, Hong</creatorcontrib><creatorcontrib>Porter, Laura H.</creatorcontrib><creatorcontrib>Frydenberg, Mark</creatorcontrib><creatorcontrib>Kourambas, John</creatorcontrib><creatorcontrib>Appu, Sree</creatorcontrib><creatorcontrib>Poole, Christine</creatorcontrib><creatorcontrib>Beardsley, Emma K.</creatorcontrib><creatorcontrib>Ryan, Andrew</creatorcontrib><creatorcontrib>Norden, Sam</creatorcontrib><creatorcontrib>Papargiris, Melissa M.</creatorcontrib><creatorcontrib>Risbridger, Gail P.</creatorcontrib><creatorcontrib>Taylor, Renea A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; 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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 75:1475–1483, 2015. © 2015 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>26177841</pmid><doi>10.1002/pros.23039</doi><tpages>9</tpages></addata></record>
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subjects Aged
Aged, 80 and over
androgen
Animals
castrate‐resistance
Heterografts
Humans
Male
Mice
Neoplasm Transplantation - methods
prostate cancer
Prostatic Neoplasms - pathology
Prostatic Neoplasms - surgery
Transplantation, Heterologous - methods
Transurethral Resection of Prostate
TURP
xenograft
title Establishment of primary patient‐derived xenografts of palliative TURP specimens to study castrate‐resistant prostate cancer
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