Epithelial-restricted gene profile of primary cultures from human prostate tumors

A molecular approach to predict clinical behavior of prostate cancer

Simona Nanni, Carmen Priolo, Annalisa Grasselli, Manuela D'Eletto, Roberta Merola, Fabiola Moretti, Michele Gallucci, Piero De Carli, Steno Sentinelli, Anna Maria Cianciulli, Marcelle Mottolese, Paolo Carlini, Diego Arcelli, Mauro Helmer-Citterich, Carlo Gaetano, Massimo Loda, Alfredo Pontecorvi, Silvia Bacchetti, Ada Sacchi, Antonella Farsetti

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

The histopathologic and molecular heterogeneity of prostate cancer and the limited availability of human tumor tissue make unraveling the mechanisms of prostate carcinogenesis a challenging task. Our goal was to develop an ex vivo model that could be reliably used to define a prognostic signature based on gene expression profiling of cell cultures that maintained the tumor phenotype. To this end, we derived epithelial cultures from tissue explanted from 59 patients undergoing radical prostatectomy or cistoprostatectomy because of prostate benign hyperplasia/prostate cancer or bladder carcinoma. Patient selection criteria were absence of hormonal neoadjuvant treatment before surgery and diagnosis of clinically localized disease. Using this unique experimental material, we analyzed expression of 22,500 transcripts on the Affymetrix Human U133A GeneChip platform (Affymetrix, Inc., High Wycombe, United Kingdom). Cultures from normal/ hyperplastic tissues with a prevalent luminal phenotype and from normal prostate epithelial tissue with basal phenotype (PrEC) served as controls. We have established a large number of prostate primary cultures highly enriched in the secretory phenotype. From them, we derived an epithelial-restricted transcriptional signature that (a) differentiated normal from tumor cells and (b) clearly separated cancer-derived lines into two distinct groups, which correlated with indolent or aggressive clinical behavior of the disease. Our findings provide (a) a method to expand human primary prostate carcinoma cells with a luminal phenotype, (b) a powerful experimental model to study primary prostate cancer biology, and (c) a novel means to characterize these tumors from a molecular genetic standpoint for prognostic and/or predictive purposes.

Original languageEnglish
Pages (from-to)79-92
Number of pages14
JournalMolecular Cancer Research
Volume4
Issue number2
DOIs
Publication statusPublished - Feb 2006

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Prostate
Prostatic Neoplasms
Phenotype
Genes
Neoplasms
Patient Selection
Epithelium
Carcinoma
Neoadjuvant Therapy
Gene Expression Profiling
Prostatectomy
Urinary Bladder Neoplasms
Hyperplasia
Molecular Biology
Carcinogenesis
Theoretical Models
Cell Culture Techniques

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Epithelial-restricted gene profile of primary cultures from human prostate tumors : A molecular approach to predict clinical behavior of prostate cancer. / Nanni, Simona; Priolo, Carmen; Grasselli, Annalisa; D'Eletto, Manuela; Merola, Roberta; Moretti, Fabiola; Gallucci, Michele; De Carli, Piero; Sentinelli, Steno; Cianciulli, Anna Maria; Mottolese, Marcelle; Carlini, Paolo; Arcelli, Diego; Helmer-Citterich, Mauro; Gaetano, Carlo; Loda, Massimo; Pontecorvi, Alfredo; Bacchetti, Silvia; Sacchi, Ada; Farsetti, Antonella.

In: Molecular Cancer Research, Vol. 4, No. 2, 02.2006, p. 79-92.

Research output: Contribution to journalArticle

Nanni, S, Priolo, C, Grasselli, A, D'Eletto, M, Merola, R, Moretti, F, Gallucci, M, De Carli, P, Sentinelli, S, Cianciulli, AM, Mottolese, M, Carlini, P, Arcelli, D, Helmer-Citterich, M, Gaetano, C, Loda, M, Pontecorvi, A, Bacchetti, S, Sacchi, A & Farsetti, A 2006, 'Epithelial-restricted gene profile of primary cultures from human prostate tumors: A molecular approach to predict clinical behavior of prostate cancer', Molecular Cancer Research, vol. 4, no. 2, pp. 79-92. https://doi.org/10.1158/1541-7786.MCR-05-0098
Nanni, Simona ; Priolo, Carmen ; Grasselli, Annalisa ; D'Eletto, Manuela ; Merola, Roberta ; Moretti, Fabiola ; Gallucci, Michele ; De Carli, Piero ; Sentinelli, Steno ; Cianciulli, Anna Maria ; Mottolese, Marcelle ; Carlini, Paolo ; Arcelli, Diego ; Helmer-Citterich, Mauro ; Gaetano, Carlo ; Loda, Massimo ; Pontecorvi, Alfredo ; Bacchetti, Silvia ; Sacchi, Ada ; Farsetti, Antonella. / Epithelial-restricted gene profile of primary cultures from human prostate tumors : A molecular approach to predict clinical behavior of prostate cancer. In: Molecular Cancer Research. 2006 ; Vol. 4, No. 2. pp. 79-92.
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