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Gene profiling of primary cultures from human prostate tumors

ABSTRACT: The histopathological 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 utilized 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 neo-adjuvant 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 Gene Chips platform. 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: 1) differentiated normal from tumor cells; and 2) clearly separated cancer derived lines into two distinct groups which correlated with indolent and aggressive clinical behavior of the disease. Our findings provide:1) a method to expand human primary prostate carcinoma cells with a luminal phenotype; 2) a powerful experimental model to study primary prostate cancer biology; and 3) a novel means to characterize these tumors from a molecular genetic standpoint for prognostic and/or predictive purposes. Keywords: prostate cancer; gene profile; primary cultures; prognosis; molecular pathology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE3868 | GEO | 2006/03/09

SECONDARY ACCESSION(S): PRJNA94105

REPOSITORIES: GEO

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Project description:Prostate primary epithelial and stromal cells were isolated from normal donorhuman prostate tissue and patient prostate tumors (>Gleason 8) using in vitroselective media conditions and differential substrate adhesion properties.Tumor cells specific to the prostate epithelial cell component attached tomatrigel while epithelial cells from donors preferentially attached to gelatinsubstrate. The prostate tumor cells did not proliferate over time in culturebut cells of normal epithelial phenotype in comparison to the donor tissueeventually emerged from this cell compartment. The epithelial componentof both donor and tumor specimens produced stem cell colonies thatexpressed OCT4 in growth factor reduced media but subsequently formedembryoid bodies in hanging drop cultures which differentiated into multiplegerm line lineages under the influence of growth factors. To determineif prostate tumor-derived stem cells were capable of forming tumors invivo, we compared the behavior of the donor and tumor stem cells aftertransplantation as tissue recombinants under the renal capsule of SCID micein the presence of rat urogenital mesenchyme (rUGM). Stem cells from bothdonor and tumor sources produced glandular structures that secreted prostatespecific antigen (PSA) while no glandular structures were formed from tissue recombinants of normal epithelial or tumor epithelial cells plus rUGM or fromrUGM alone. Serial transplantation of the stem cell recombinants from tumor specimens yielded subrenal structures reflecting an abundance of glandswith morphological features typical of Prostatic Intraepithelial Neoplasia(PIN). In order to determine whether intrinsic differences existed amongthe donor-derived and tumor-derived stem cells, array based microRNAexpression profiling was performed on all cell types obtained after in vitro isolation. Sample Labeling Key: PC-Prostate Cancer PD-Prostate Donor (Normal Tissue) DNE-Donor Normal Epithelial NS-Donor Normal Stem TNE-Tumor Normal Epithelial TE-Tumor Epithelial (TNE and TE samples with corresponding numbers are matched pairs) TS-Tumor Stem Cell S-Stromal PC 73 TNE was run in all 6 batches as a control for batch effect. The number in parentheses corresponds with the batch the sample was run in.

Project description:Prostate primary epithelial and stromal cells were isolated from normal donorhuman prostate tissue and patient prostate tumors (>Gleason 8) using in vitroselective media conditions and differential substrate adhesion properties.Tumor cells specific to the prostate epithelial cell component attached tomatrigel while epithelial cells from donors preferentially attached to gelatinsubstrate. The prostate tumor cells did not proliferate over time in culturebut cells of normal epithelial phenotype in comparison to the donor tissueeventually emerged from this cell compartment. The epithelial componentof both donor and tumor specimens produced stem cell colonies thatexpressed OCT4 in growth factor reduced media but subsequently formedembryoid bodies in hanging drop cultures which differentiated into multiplegerm line lineages under the influence of growth factors. To determineif prostate tumor-derived stem cells were capable of forming tumors invivo, we compared the behavior of the donor and tumor stem cells aftertransplantation as tissue recombinants under the renal capsule of SCID micein the presence of rat urogenital mesenchyme (rUGM). Stem cells from bothdonor and tumor sources produced glandular structures that secreted prostatespecific antigen (PSA) while no glandular structures were formed from tissuerecombinants of normal epithelial or tumor epithelial cells plus rUGM or fromrUGM alone. Serial transplantation of the stem cell recombinants from tumorspecimens yielded subrenal structures reflecting an abundance of glands with morphological features typical of Prostatic Intraepithelial Neoplasia(PIN). In order to determine whether intrinsic differences existed amongthe donor-derived and tumor-derived stem cells, array based microRNAexpression profiling was performed on all cell types obtained after in vitro isolation. Sample Labeling Key: PC-Prostate Cancer PD-Prostate Donor (Normal Tissue) DNE-Donor Normal Epithelial NS-Donor Normal Stem TNE-Tumor Normal Epithelial TE-Tumor Epithelial (TNE and TE samples with corresponding numbers are matched pairs) TS-Tumor Stem Cell S-Stromal PC 73 TNE was run in all 6 batches as a control for batch effect. The number in parentheses corresponds with the batch the sample was run in.

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Gene profiling of primary cultures from human prostate tumors

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