Establishment and genomic characterization of mouse xenografts of human primary prostate tumors

Carmen Priolo, Michelle Agostini, Natalie Vena, Azra H. Ligon, Michelangelo Fiorentino, Eyoung Shin, Antonella Farsetti, Alfredo Pontecorvi, Ewa Sicinska, Massimo Loda

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Serum prostate-specific antigen screening has led to earlier detection and surgical treatment of prostate cancer, favoring an increasing incidence-to-mortality ratio. However, about one third of tumors that are diagnosed when still confined to the prostate can relapse within 10 years from the first treatment. The challenge is therefore to identify prognostic markers of aggressive versus indolent tumors. Although several preclinical models of advanced prostate tumors are available, a model that recapitulates the genetic and growth behavior of primary tumors is still lacking. Here, we report a complete histopathological and genomic characterization of xenografts derived from primary localized low- and high-grade human prostate tumors that were implanted under the renal capsule of immunodeficient mice. We obtained a tumor take of 56% and show that these xenografts maintained the histological as well as most genomic features of the parental tumors. Serum prostate-specific antigen levels were measurable only in tumor xenograft-bearing mice, but not in those implanted with either normal prostate tissue or in tumors that likely regressed. Finally, we show that a high proliferation rate, but not the pathological stage or the Gleason grade of the original tumor, was a fundamental prerequisite for tumor take in mice. This mouse xenograft model represents a useful preclinical model of primary prostate tumors for their biological characterization, biomarker discovery, and drug testing.

Original languageEnglish
Pages (from-to)1901-1913
Number of pages13
JournalAmerican Journal of Pathology
Volume176
Issue number4
DOIs
Publication statusPublished - Apr 2010

Fingerprint

Heterografts
Prostate
Neoplasms
Prostate-Specific Antigen
Genetic Models
Drug Discovery
Serum
Capsules
Prostatic Neoplasms
Biomarkers
Kidney
Recurrence

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Priolo, C., Agostini, M., Vena, N., Ligon, A. H., Fiorentino, M., Shin, E., ... Loda, M. (2010). Establishment and genomic characterization of mouse xenografts of human primary prostate tumors. American Journal of Pathology, 176(4), 1901-1913. https://doi.org/10.2353/ajpath.2010.090873

Establishment and genomic characterization of mouse xenografts of human primary prostate tumors. / Priolo, Carmen; Agostini, Michelle; Vena, Natalie; Ligon, Azra H.; Fiorentino, Michelangelo; Shin, Eyoung; Farsetti, Antonella; Pontecorvi, Alfredo; Sicinska, Ewa; Loda, Massimo.

In: American Journal of Pathology, Vol. 176, No. 4, 04.2010, p. 1901-1913.

Research output: Contribution to journalArticle

Priolo, C, Agostini, M, Vena, N, Ligon, AH, Fiorentino, M, Shin, E, Farsetti, A, Pontecorvi, A, Sicinska, E & Loda, M 2010, 'Establishment and genomic characterization of mouse xenografts of human primary prostate tumors', American Journal of Pathology, vol. 176, no. 4, pp. 1901-1913. https://doi.org/10.2353/ajpath.2010.090873
Priolo, Carmen ; Agostini, Michelle ; Vena, Natalie ; Ligon, Azra H. ; Fiorentino, Michelangelo ; Shin, Eyoung ; Farsetti, Antonella ; Pontecorvi, Alfredo ; Sicinska, Ewa ; Loda, Massimo. / Establishment and genomic characterization of mouse xenografts of human primary prostate tumors. In: American Journal of Pathology. 2010 ; Vol. 176, No. 4. pp. 1901-1913.
@article{0460565adc70496eb00423ddaaf96eb2,
title = "Establishment and genomic characterization of mouse xenografts of human primary prostate tumors",
abstract = "Serum prostate-specific antigen screening has led to earlier detection and surgical treatment of prostate cancer, favoring an increasing incidence-to-mortality ratio. However, about one third of tumors that are diagnosed when still confined to the prostate can relapse within 10 years from the first treatment. The challenge is therefore to identify prognostic markers of aggressive versus indolent tumors. Although several preclinical models of advanced prostate tumors are available, a model that recapitulates the genetic and growth behavior of primary tumors is still lacking. Here, we report a complete histopathological and genomic characterization of xenografts derived from primary localized low- and high-grade human prostate tumors that were implanted under the renal capsule of immunodeficient mice. We obtained a tumor take of 56{\%} and show that these xenografts maintained the histological as well as most genomic features of the parental tumors. Serum prostate-specific antigen levels were measurable only in tumor xenograft-bearing mice, but not in those implanted with either normal prostate tissue or in tumors that likely regressed. Finally, we show that a high proliferation rate, but not the pathological stage or the Gleason grade of the original tumor, was a fundamental prerequisite for tumor take in mice. This mouse xenograft model represents a useful preclinical model of primary prostate tumors for their biological characterization, biomarker discovery, and drug testing.",
author = "Carmen Priolo and Michelle Agostini and Natalie Vena and Ligon, {Azra H.} and Michelangelo Fiorentino and Eyoung Shin and Antonella Farsetti and Alfredo Pontecorvi and Ewa Sicinska and Massimo Loda",
year = "2010",
month = "4",
doi = "10.2353/ajpath.2010.090873",
language = "English",
volume = "176",
pages = "1901--1913",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Establishment and genomic characterization of mouse xenografts of human primary prostate tumors

AU - Priolo, Carmen

AU - Agostini, Michelle

AU - Vena, Natalie

AU - Ligon, Azra H.

AU - Fiorentino, Michelangelo

AU - Shin, Eyoung

AU - Farsetti, Antonella

AU - Pontecorvi, Alfredo

AU - Sicinska, Ewa

AU - Loda, Massimo

PY - 2010/4

Y1 - 2010/4

N2 - Serum prostate-specific antigen screening has led to earlier detection and surgical treatment of prostate cancer, favoring an increasing incidence-to-mortality ratio. However, about one third of tumors that are diagnosed when still confined to the prostate can relapse within 10 years from the first treatment. The challenge is therefore to identify prognostic markers of aggressive versus indolent tumors. Although several preclinical models of advanced prostate tumors are available, a model that recapitulates the genetic and growth behavior of primary tumors is still lacking. Here, we report a complete histopathological and genomic characterization of xenografts derived from primary localized low- and high-grade human prostate tumors that were implanted under the renal capsule of immunodeficient mice. We obtained a tumor take of 56% and show that these xenografts maintained the histological as well as most genomic features of the parental tumors. Serum prostate-specific antigen levels were measurable only in tumor xenograft-bearing mice, but not in those implanted with either normal prostate tissue or in tumors that likely regressed. Finally, we show that a high proliferation rate, but not the pathological stage or the Gleason grade of the original tumor, was a fundamental prerequisite for tumor take in mice. This mouse xenograft model represents a useful preclinical model of primary prostate tumors for their biological characterization, biomarker discovery, and drug testing.

AB - Serum prostate-specific antigen screening has led to earlier detection and surgical treatment of prostate cancer, favoring an increasing incidence-to-mortality ratio. However, about one third of tumors that are diagnosed when still confined to the prostate can relapse within 10 years from the first treatment. The challenge is therefore to identify prognostic markers of aggressive versus indolent tumors. Although several preclinical models of advanced prostate tumors are available, a model that recapitulates the genetic and growth behavior of primary tumors is still lacking. Here, we report a complete histopathological and genomic characterization of xenografts derived from primary localized low- and high-grade human prostate tumors that were implanted under the renal capsule of immunodeficient mice. We obtained a tumor take of 56% and show that these xenografts maintained the histological as well as most genomic features of the parental tumors. Serum prostate-specific antigen levels were measurable only in tumor xenograft-bearing mice, but not in those implanted with either normal prostate tissue or in tumors that likely regressed. Finally, we show that a high proliferation rate, but not the pathological stage or the Gleason grade of the original tumor, was a fundamental prerequisite for tumor take in mice. This mouse xenograft model represents a useful preclinical model of primary prostate tumors for their biological characterization, biomarker discovery, and drug testing.

UR - http://www.scopus.com/inward/record.url?scp=77950592442&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950592442&partnerID=8YFLogxK

U2 - 10.2353/ajpath.2010.090873

DO - 10.2353/ajpath.2010.090873

M3 - Article

C2 - 20167861

AN - SCOPUS:77950592442

VL - 176

SP - 1901

EP - 1913

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 4

ER -