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 language | English |
|---|---|
| Pages (from-to) | 79-92 |
| Number of pages | 14 |
| Journal | Molecular Cancer Research |
| Volume | 4 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2006 |
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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 journal › Article
}
TY - JOUR
T1 - Epithelial-restricted gene profile of primary cultures from human prostate tumors
T2 - A molecular approach to predict clinical behavior of prostate cancer
AU - Nanni, Simona
AU - Priolo, Carmen
AU - Grasselli, Annalisa
AU - D'Eletto, Manuela
AU - Merola, Roberta
AU - Moretti, Fabiola
AU - Gallucci, Michele
AU - De Carli, Piero
AU - Sentinelli, Steno
AU - Cianciulli, Anna Maria
AU - Mottolese, Marcelle
AU - Carlini, Paolo
AU - Arcelli, Diego
AU - Helmer-Citterich, Mauro
AU - Gaetano, Carlo
AU - Loda, Massimo
AU - Pontecorvi, Alfredo
AU - Bacchetti, Silvia
AU - Sacchi, Ada
AU - Farsetti, Antonella
PY - 2006/2
Y1 - 2006/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33645123129&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645123129&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-05-0098
DO - 10.1158/1541-7786.MCR-05-0098
M3 - Article
C2 - 16513839
AN - SCOPUS:33645123129
VL - 4
SP - 79
EP - 92
JO - Molecular Cancer Research
JF - Molecular Cancer Research
SN - 1541-7786
IS - 2
ER -