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  PCa cell line

Overall DesignA total of 221 single candidate prostate CTCs were isolated from 18 patients with metastatic prostate cancer and 4 patients with localized prostate cancer. Of these, 133 cells (60%) had RNA of sufficient quality for amplification and next generation RNA sequencing, and 122 (55%) had >100,000 uniquely aligned sequencing reads. In addition to candidate CTCs, we also obtained comprehensive transcriptomes for 12 bulk primary prostate cancers (macrodissected for >70% tumor content), 30 single cells derived from four different prostate cancer cell lines, and 5 patient-derived leukocyte controls. The leukocytes were readily distinguished by their expression of hematopoietic lineage markers and served to exclude any CTCs with potentially contaminating signals. Strict expression thresholds were used to define lineage-confirmed CTCs, scored by prostate lineage-specific genes (PSA, PSMA, AMACR, AR) and standard epithelial markers (KRT7, KRT8, KRT18, KRT19, EpCAM). 28 cells were excluded given the presence of leukocyte transcripts suggestive of cellular contamination or misidentification during selection, and 17 cells were excluded given low expression of both prostate lineage-specific genes and 5 standard epithelial markers. The remaining 77 cells, defined as lineage-confirmed CTCs, displayed expression of either prostate lineage-specific or epithelial genes, and low expression of leukocyte-specific genes, consistent with their tumor of origin.
SummaryProstate cancer is initially responsive to androgen deprivation, but the effectiveness of androgen receptor (AR) inhibitors in recurrent disease is variable. Biopsy of bone metastases is challenging, hence sampling circulating tumor cells (CTCs) may reveal drug resistance mechanisms. We established single cell RNA-sequencing profiles of 77 intact CTCs isolated from 13 patients (mean 6 CTCs/patient) using microfluidic enrichment. Single CTCs from each individual display considerable heterogeneity, including expression of AR gene mutations and splicing variants. Retrospective analysis of CTCs from patients progressing on AR inhibitor, compared with untreated cases indicates activation of noncanonical Wnt signaling (P=0.0064). Ectopic expression of Wnt5a in prostate cancer cells attenuates the antiproliferative effect of AR inhibition, while its suppression in drug-resistant cells restores partial sensitivity, a correlation also evident in an established mouse model. Thus, single cell analysis of prostate CTCs reveals heterogeneity in signaling pathways that could contribute to treatment failure.
Dataset viewGSE67980
PMID26383955

Samples in PCa cell line

Displaying 1-10 of 30 results.
SeriesSampleInstrumentOrganismTitleCell Source
GSE67980GSM1660207AB 5500xl Genetic AnalyzerHomo sapiensDU145.1PCa cell line
GSE67980GSM1660208AB 5500xl Genetic AnalyzerHomo sapiensDU145.2PCa cell line
GSE67980GSM1660209AB 5500xl Genetic AnalyzerHomo sapiensDU145.3PCa cell line
GSE67980GSM1660210AB 5500xl Genetic AnalyzerHomo sapiensDU145.4PCa cell line
GSE67980GSM1660211AB 5500xl Genetic AnalyzerHomo sapiensDU145.5PCa cell line
GSE67980GSM1660212AB 5500xl Genetic AnalyzerHomo sapiensLNCaP.1PCa cell line
GSE67980GSM1660213AB 5500xl Genetic AnalyzerHomo sapiensLNCaP.2PCa cell line
GSE67980GSM1660214AB 5500xl Genetic AnalyzerHomo sapiensLNCaP.3PCa cell line
GSE67980GSM1660215AB 5500xl Genetic AnalyzerHomo sapiensLNCaP.4PCa cell line
GSE67980GSM1660216AB 5500xl Genetic AnalyzerHomo sapiensLNCaP.5PCa cell line

Gene rank in PCa cell line

Displaying 1-10 of 18557 results.
Rank orderGene SymbolEnsembl ID
1EEF1A1ENSG00000156508
2RPLP0ENSG00000089157
3GNB2L1
4EEF1GENSG00000254772
5RPL3ENSG00000100316
6TPT1ENSG00000133112
7RPL4ENSG00000174444
8RPL7ENSG00000147604
9RPS6ENSG00000137154
10HSP90AA1ENSG00000080824