Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA343124 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4246370.fastq.gz | Fastqsanger.gz | |||
| SRR4246380.fastq.gz | Fastqsanger.gz | |||
| SRR4246390.fastq.gz | Fastqsanger.gz | |||
| SRR4246400.fastq.gz | Fastqsanger.gz | |||
| SRR4246410.fastq.gz | Fastqsanger.gz |
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Project description:Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, we undertook RNA sequencing of circulating tumor cells (CTCs) obtained from blood samples of women with metastatic estrogen receptor (ER)+ breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is Androgen Receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splicing variant AR-v7. AR expression within CTCs is correlated with the duration of treatment with aromatase inhibitors, suggesting that it may contribute to acquired resistance to anti-estrogen therapy. In an established breast cancer xenograft model, a bone-tropic derivative displays increased AR expression, whose genetic or pharmacologic suppression reduces metastases to bone but not to lungs. Together, these observations identify AR signaling in CTCs from women with bone-predominant ER+ breast cancer, and provide a rationale for testing androgen inhibitors in this subset of patients.
2018-02-19 | GSE86978 | GEO
Project description:Prostate 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.
2015-09-17 | GSE67980 | GEO
Project description:Prostate 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. A 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.
2015-09-17 | E-GEOD-67980 | biostudies-arrayexpress
Project description:Metastasis is responsible for the vast majority of breast cancer related deaths. Metastatic breast cancer (MBC) is inherently different than primary breast cancer (BC), evolving under selection pressure at different organ sites or during systemic therapy. The current ASCO guidelines call for biopsy of a metastatic site to guide decision making for systemic therapy. Yet, biopsies of macro metastasis are oftentimes not feasible in the clinical setting. Circulating tumor cells (CTCs) have been shown to be prognostic in MBC, but their use as clinical biomarker beyond CTC enumeration has been limited. A better understanding of CTC-biology compared to metastasis may shed light on treatment opportunities and help advance the application of CTCs as liquid biopsies in clinical practice. The ANGLE Parsortix system is a microfluidics device that separates CTCs based on size and deformability, without the need for cell-surface marker selection. Our lab has previously demonstrated the feasibility of gene expression profiling of rare CTCs. Here, we evaluated whether whole transcriptome sequencing (RNA Seq) gene expression profiling of ANGLE Parsortix isolated CTCs may serve as a surrogate for biopsies of macro metastases. CTCs from 21 MBC patients were enumerated and captured from 10mL peripheral blood (PB) via the ANGLE Parsortix system. RNA Seq was performed on fresh metastatic tumor biopsies (mets), CTCs and peripheral blood from all patients. Biopsy sites included: skin (n=1), lung (n=1), pleural effusion (n=5), pericardial effusion (n=1), breast (n=3), lymph node (n=2), brain (n=4), liver (n=1), ascites (n=3), cerebrospinal fluid (n=2) and bone (n=1). 19/21 patients were included in subsequent data analysis. We present the whole transcriptomic landscape of CTCs with comparison to metastases and peripheral blood all acquired prior to treatment of Stage IV breast cancer. Multiple genes, including oncogenes, breast epithelial, mesenchymal genes and cancer stem cell genes were found with higher expression in CTCs versus metastases. When focusing on 66 known potentially clinically actionable genes in breast cancer, represented by 7 molecular signaling pathways, CTCs did not show significantly different patterns of expression versus mets compared to PB. RNA Seq of CTCs may be utilized to identify alterations in MBC patients that are potentially clinically actionable.
2022-05-01 | GSE113890 | GEO
Project description:Circulating tumor cells (CTCs) and disseminated tumour cells with mesenchymal traits are difficult to detect by epithelial marker proteins. Particularly, triple negative breast cancers (TNBC) that are prone to therapy failure release a subpopulation of circulating tumour cells (CTCs) with mesenchymal traits. To provide tools that support their detection and analysis, the cell line BC-M1 established from disseminated tumour cells in the bone marrow of a breast cancer patient and a bone metastasis subline of MDA-MB-231 were analysed. Mass spectrometry analysis revealed high levels of CUB domain-containing protein 1 (CDCP1) in BC-M1. CDCP1 was found in other carcinoma cell lines (MDA-MB-231, MDA-MB-468) and other DTC cell lines (LC-M1, PC-E1) as well. Peripheral blood mononuclear cells were virtually negative for CDCP1 by Western Blot and immunofluorescent staining. Presence of CDCP1 in CTCs was confirmed by CellSearch. Here, CDCP1 positive CTCs were detected in eight of 30 analysed breast cancer patients. For the isolation of CTCs from the blood of breast cancer patients, we established a sandwich magnetic-activated cell sorting (MACS). The extracellular domain of CDCP1 served for cell catching and the cytoplasmic domain of CDCP1 for immunofluorescent detection of CDCP1 in CTCs. We showed that the MACS approach is suitable for the isolation of EpCam/keratin negative breast cancer cells from the blood and isolated CDCP1 positive CTCs from breast cancer patients by MACS. Hence, our approach is particularly suited for the detection and isolation of CTCs from TNBC when low EpCam or keratin levels limit the application of conventional approaches.
2023-03-20 | PXD035203 | Pride
Project description:Hematogenous metastasis is initiated by a subset of circulating tumor cells (CTCs) shed from primary or metastatic tumors into the blood circulation. Thus, CTCs provide a unique patient biopsy resource to decipher the cellular subpopulations that initiate metastasis and their molecular properties. However, one crucial question is whether CTCs derived from patients recapitulate human metastatic disease in an animal model. Here, we show that CTC lines established from breast cancer patients are capable of generating metastases in mice with a pattern recapitulating most major organs from corresponding patients. To investigate the tumor microenvironment changes in different metastases, we used RNA-seq to analyze expression changes in stromal cells after tumor formation in the brain, lung and bone microenvironments relative to control stromal cells from tumor free mice.
2019-10-14 | GSE112853 | GEO
Project description:In many patients with solid tumors circulating tumor cells (CTCs), that form metastases, can be identified in peripheral blood. Detection and characterization of CTCs in cancer patients provide a unique opportunity to predict patient survival, select and monitor the efficacy of treatment as well as to gain insights into the cascade of metastatic events. Here, we describe a novel approach to identify CTC-specific molecular markers. Using an integrated platform for immunomagnetic enrichment and immunofluorescent identification of CTCs, blood samples with large numbers of CTCs were identified from patients with colorectal, prostate and breast cancers. Despite enrichment, CTCs are still outnumbered by "nonspecifically" captured leukocytes. In order to determine gene expression profile for CTCs, "background" gene expression signature of white blood cells must be taken into account. To this end, following enrichment for CTCs, RNA was also extracted from the remaining CTC-depleted blood samples. The following samples were used to generate the global expression profiles for CTCs:<br><br> 1a) SAMPLE170711SUB735: CTC-enriched blood sample from a patient with breast cancer). 3700 CTCs were identified per 7.5 ml of peripheral blood in this patient.<br> 1b) SAMPLE170712SUB735: Corresponding CTC-depleted blood sample for the above patient with breast cancer.<br> 2a) SAMPLE170829SUB750: CTC-enriched blood sample from a patient with prostate cancer. 647 CTCs were identified per 7.5 ml of peripheral blood in this patient.<br> 2b) SAMPLE170830SUB750: Corresponding CTC-depleted blood sample for the above patient with prostate cancer.<br> 3a) SAMPLE170831SUB751: CTC-enriched sample from a patient with colorectal cancer. 180 CTCs were identified per 7.5 ml of peripheral blood in this patient.<br> 3b) SAMPLE170832SUB751: Corresponding CTC-depleted blood sample for the above patient with colorectal cancer.
2005-06-30 | E-MEXP-136 | biostudies-arrayexpress
Project description:Bone is the primary site of breast cancer metastasis and complications associated with bone metastases can lead to a significantly decreased quality of life in these patients. Thus, it is essential to gain a better understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases. Methods: To search for novel molecular mediators that influence breast cancer bone metastasis, we generated gene expression profiles from laser capture micro-dissected trephine biopsies of both breast cancer bone metastases and primary breast tumors that metastasized to bone. Bioinformatics analysis identified genes that are differentially expressed in breast cancer bone metastases compared to primary mammary tumors. Results: ABCC5, an ATP-dependent transporter, was found to be overexpressed in breast cancer osseous metastases relative to primary mammary tumors. In addition, ABCC5 was significantly up-regulated in human and mouse breast cancer cell lines with high bone-metastatic potential. Stable knockdown of ABCC5 significant reduced bone metastatic burden and osteolytic bone destruction in mice. The decrease in osteolysis was further associated with diminished osteoclast numbers. Conclusions: Our data, for the first time, suggests that ABCC5 functions as a mediator of breast cancer skeletal metastasis. ABCC5 expression in breast cancer cells is important for the efficient bone resorption mediated by osteoclasts. Hence, ABCC5 may be a potential therapeutic target for breast cancer bone metastasis. primary breast tumors vs. bone trephine biopsies
2012-11-09 | E-GEOD-39494 | biostudies-arrayexpress