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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 21-30 of 30 results.
SeriesSampleInstrumentOrganismTitleCell Source
GSE67980GSM1660227AB 5500xl Genetic AnalyzerHomo sapiensPC3.1PCa cell line
GSE67980GSM1660228AB 5500xl Genetic AnalyzerHomo sapiensPC3.2PCa cell line
GSE67980GSM1660229AB 5500xl Genetic AnalyzerHomo sapiensPC3.3PCa cell line
GSE67980GSM1660230AB 5500xl Genetic AnalyzerHomo sapiensPC3.4PCa cell line
GSE67980GSM1660231AB 5500xl Genetic AnalyzerHomo sapiensPC3.5PCa cell line
GSE67980GSM1660232AB 5500xl Genetic AnalyzerHomo sapiensVCaP.1PCa cell line
GSE67980GSM1660233AB 5500xl Genetic AnalyzerHomo sapiensVCaP.2PCa cell line
GSE67980GSM1660234AB 5500xl Genetic AnalyzerHomo sapiensVCaP.3PCa cell line
GSE67980GSM1660235AB 5500xl Genetic AnalyzerHomo sapiensVCaP.4PCa cell line
GSE67980GSM1660236AB 5500xl Genetic AnalyzerHomo sapiensVCaP.5PCa cell line

Gene rank in PCa cell line

Displaying 18511-18520 of 18557 results.
Rank orderGene SymbolEnsembl ID
18511WNT16ENSG00000002745
18512WNT3AENSG00000154342
18513WNT8AENSG00000061492
18514WT1-ASENSG00000183242
18515XCL1ENSG00000143184
18516XCR1ENSG00000173578
18517XIRP1ENSG00000168334
18518XISTENSG00000229807
18519XKR4ENSG00000206579
18520XKRXENSG00000182489