Epithelial-restricted gene profile of primary cultures from human prostate tumors: a molecular approach to predict clinical behavior of prostate cancer.
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.
Nanni
Simona
S
Molecular Oncogenesis Laboratory, Department of Experimental Oncology, Regina Elena Cancer Institute-Experimental Research Center, Via delle Messi d'Oro 156, 00158 Rome, Italy.
Priolo
Carmen
C
Grasselli
Annalisa
A
D'Eletto
Manuela
M
Merola
Roberta
R
Moretti
Fabiola
F
Gallucci
Michele
M
De Carli
Piero
P
Sentinelli
Steno
S
Cianciulli
Anna Maria
AM
Mottolese
Marcella
M
Carlini
Paolo
P
Arcelli
Diego
D
Helmer-Citterich
Mauro
M
Gaetano
Carlo
C
Loda
Massimo
M
Pontecorvi
Alfredo
A
Bacchetti
Silvia
S
Sacchi
Ada
A
Farsetti
Antonella
A
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011379:Prognosis; D011467:Prostate / Q000378:metabolism; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000601:surgery; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor