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Gene expression down-regulation in prostate tumor-associated stromal cells involves organ-specific genes

ABSTRACT: The prostate stroma is a key mediator of epithelial differentiation and development, and potentially plays a role in the initiation and progression of prostate cancer. Isolation and characterization of viable populations of the constituent cell types of prostate tumors could provide valuable insight into the biology of cancer. The CD90+ stromal fibromuscular cells from tumor specimens were isolated by cell-sorting and analyzed by DNA microarray. Dataset analysis was used to compare gene expression between normal and tumor-associated reactive stromal cells. Reactive stroma is characterized by smooth muscle differentiation, prostate down-regulation of SPOCK3, MSMB, CXCL13, and PAGE4, bladder down-regulation of TRPA1, HSD17B2, IL24, and SALL1, and an up-regulation of CXC-chemokines. This study identified a group of differentially expressed genes in CD90+ reactive stromal cells that are potentially involved in organ development and smooth muscle cell differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE17906 | GEO | 2009/09/09

SECONDARY ACCESSION(S): PRJNA119977

REPOSITORIES: GEO

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Project description:The prostate stroma is a key mediator of epithelial differentiation and development, and potentially plays a role in the initiation and progression of prostate cancer. Isolation and characterization of viable populations of the constituent cell types of prostate tumors could provide valuable insight into the biology of cancer. The CD90+ stromal fibromuscular cells from tumor specimens were isolated by cell-sorting and analyzed by DNA microarray. Dataset analysis was used to compare gene expression between normal and tumor-associated reactive stromal cells. Reactive stroma is characterized by smooth muscle differentiation, prostate down-regulation of SPOCK3, MSMB, CXCL13, and PAGE4, bladder down-regulation of TRPA1, HSD17B2, IL24, and SALL1, and an up-regulation of CXC-chemokines. This study identified a group of differentially expressed genes in CD90+ reactive stromal cells that are potentially involved in organ development and smooth muscle cell differentiation. Experiment Overall Design: A total of 15 arrays were run for the following sample types obtained from 10 patients: Experiment Overall Design: 2 CD90+ prostate tumor-associated stromal: Experiment Overall Design: Patient 1: CP_Str_08-028_CD90posi Experiment Overall Design: Patient 2: 08-032_CP_strom_CD90posi Experiment Overall Design: 2 CD13+ normal bladder stromal: Experiment Overall Design: Patient 3: 06-125_NB_CD13posi Experiment Overall Design: Patient 4: 06-070_NB_str_CD13posi Experiment Overall Design: 1 CD13+ bladder tumor-associated stromal: Experiment Overall Design: Patient 5: 07-008_CB_str_CD13posi Experiment Overall Design: 5 whole tissue prostate cancer and 5 normal tissue from matched pairs: Experiment Overall Design: Patient 6: 05-206_CaP, 05-206_NP Experiment Overall Design: Patient 7: 05-213_CaP, 05-213_NP Experiment Overall Design: Patient 8: 05-214_CaP, 05-214_NP Experiment Overall Design: Patient 9: 05-218_CaP, 05-218_NP Experiment Overall Design: Patient 10: 05-220_CaP, 05-220_NP Experiment Overall Design: Additionally, 8 arrays were run for the following sample types obtained from 7 patients: Experiment Overall Design: 5 CD49a+ normal prostate stromal (PMID 16638148): Experiment Overall Design: Patient 1: CD49a_01-26-04 Experiment Overall Design: Patient 2: CD49a_03-23-04 Experiment Overall Design: Patient 3: CD49a_03-04-04 Experiment Overall Design: Patient 4: CD49a-1_06-02-04 Experiment Overall Design: Patient 5: CD49a-4_06-02-04 Experiment Overall Design: 3 CD26+ prostate cancer (2 biological replicates, 1 sample run twice): Experiment Overall Design: Patient 6: 05-179_CD26t Experiment Overall Design: Patient 6: 05-179_CD26t_2 Experiment Overall Design: Patient 7: 08-032_CP_epi_CD26posi Experiment Overall Design: The following two prostate cancer samples were also included in the analyses: Experiment Overall Design: CD26+ cancer cell, replicate 1 Experiment Overall Design: CD26+ cancer cell, replicate 2 Experiment Overall Design: The tissue samples consisted of prostate tissue specimens obtained from patients undergoing radical prostatectomy under approval by the University of Washington Institutional Review Board. The same approach was used for both cancer-free and cancer-enriched (where at least 85% of the cells in the corresponding frozen section were of cancer) samples. To obtain bladder stromal cells for analysis, tissue specimens were obtained from cystoprostatectomy surgeries. For cell sorting, the collected specimens were processed within hours. Cell types were sorted using monoclonal antibodies specific for tumor-associated prostate stromal cells (CD90), tumor-associated bladder stromal cells (CD13) and normal bladder stromal cells (CD13) with MACS.

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Gene expression down-regulation in prostate tumor-associated stromal cells involves organ-specific genes

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