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.
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Mitchell G
authors.initials: MG
authors.lastname: Lawrence
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.|Department of Oncology, Monash Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Pook
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Laura H
authors.initials: LH
authors.lastname: Porter
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.|Department of Urology, Monash Medical Centre, Clayton, Victoria, Australia.|Department of Surgery, Monash University, Clayton, Victoria, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Frydenberg
authors.affiliation: Department of Urology, Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Kourambas
authors.affiliation: Department of Urology, Monash Medical Centre, Clayton, Victoria, Australia.|Department of Surgery, Monash University, Clayton, Victoria, Australia.
authors.forename: Sree
authors.initials: S
authors.lastname: Appu
authors.affiliation: Department of Urology, Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: Christine
authors.initials: C
authors.lastname: Poole
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Emma K
authors.initials: EK
authors.lastname: Beardsley
authors.affiliation: TissuPath Pathology, Melbourne, Mount Waverley, Victoria, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Ryan
authors.affiliation: TissuPath Pathology, Melbourne, Mount Waverley, Victoria, Australia.
authors.forename: Sam
authors.initials: S
authors.lastname: Norden
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Papargiris
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Gail P
authors.initials: GP
authors.lastname: Risbridger
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria, Australia.
authors.forename: Renea A
authors.initials: RA
authors.lastname: Taylor
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation / Q000379:methods*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery; D014183:Transplantation, Heterologous / Q000379:methods*; D020728:Transurethral Resection of Prostate
keywords: TURP; androgen; castrate-resistance; prostate cancer; xenograft