title: Spheroid culture of LuCaP 147 as an authentic preclinical model of prostate cancer subtype with SPOP mutation and hypermutator phenotype.
abstract: LuCaP serially transplantable xenografts are valuable preclinical models of locally advanced or metastatic prostate cancer. For the first time, we recently succeeded in establishing and serially passaging spheroid cultures of several LuCaP xenografts. Here, we characterized in depth the molecular and cellular phenotype of LuCaP 147 cultures and found faithful retention of the characteristics of the original xenograft, including immunophenotype, genetic fidelity, gene expression profile and responsiveness to androgen. Furthermore, we demonstrated capabilities for high-throughput drug screening and that anti-cancer agents induced cell cycle arrest and apoptosis in spheroid cultures. Finally, we showed that cells formed tumors when re-introduced into mice, providing an authentic in vitro-in vivo preclinical model of a subtype of prostate cancer with a hypermutator phenotype and an SPOP mutation.
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Urology and Pediatric Urology, University of Saarland, Homburg, Saar, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Saar
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Rosalie
authors.initials: R
authors.lastname: Nolley
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Young
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Ilsa
authors.initials: I
authors.lastname: Coleman
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Nelson
authors.affiliation: Department of Urology, University of Washington, Puget Sound VA Health Care System, Seattle, WA 98195, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Vessella
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: dpeehl@stanford.edu.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Peehl
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D064593:Heterografts; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D051379:Mice; D009154:Mutation; D009570:Nitriles / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D012097:Repressor Proteins / Q000235:genetics*; D018874:Spheroids, Cellular; D014105:Tosyl Compounds / Q000494:pharmacology; D043743:Ubiquitin-Protein Ligase Complexes
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014105:Tosyl Compounds; D015741:Metribolone; C053541:bicalutamide; C509762:Spop protein, mouse; D043743:Ubiquitin-Protein Ligase Complexes
keywords: Drug testing; Preclinical model; Prostate cancer; SPOP; Spheroids