Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA225522 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Clusters of circulating tumor cells (CTC-clusters) are present in the blood of patients with cancer but their contribution to metastasis is not well defined. Here, we first use mouse models to demonstrate that breast cancer cells injected intravascularly as clusters are more prone to survive and colonize the lungs than single cells. Primary mammary tumors comprised of tagged cells give rise to oligoclonal CTC-clusters, with 50-fold increased metastatic potential, compared with single CTCs. Using intravital imaging and in vivo flow cytometry, CTC-clusters are visualized in the tumor circulation, and they demonstrate rapid clearance in peripheral vessels. In patients with breast cancer, presence of CTC-clusters is correlated with decreased progression-free survival. RNA sequencing identifies the cell junction protein plakoglobin as most differentially expressed between clusters and single human breast CTCs. Expression of plakoglobin is required for efficient CTC-cluster formation and breast cancer metastasis in mice, while its expression is associated with diminished metastasis-free survival in breast cancer patients. Together, these observations suggest that plakoglobin-enriched primary tumor cells break off into the vasculature as CTC-clusters, with greatly enhanced metastasis propensity. RNA-seq from 29 samples (15 pools of single CTCs and 14 CTC-clusters) isolated from 10 breast cancer patients
2014-07-11 | E-GEOD-51827 | biostudies-arrayexpress
Project description:Clusters of circulating tumor cells (CTC-clusters) are present in the blood of patients with cancer but their contribution to metastasis is not well defined. Here, we first use mouse models to demonstrate that breast cancer cells injected intravascularly as clusters are more prone to survive and colonize the lungs than single cells. Primary mammary tumors comprised of tagged cells give rise to oligoclonal CTC-clusters, with 50-fold increased metastatic potential, compared with single CTCs. Using intravital imaging and in vivo flow cytometry, CTC-clusters are visualized in the tumor circulation, and they demonstrate rapid clearance in peripheral vessels. In patients with breast cancer, presence of CTC-clusters is correlated with decreased progression-free survival. RNA sequencing identifies the cell junction protein plakoglobin as most differentially expressed between clusters and single human breast CTCs. Expression of plakoglobin is required for efficient CTC-cluster formation and breast cancer metastasis in mice, while its expression is associated with diminished metastasis-free survival in breast cancer patients. Together, these observations suggest that plakoglobin-enriched primary tumor cells break off into the vasculature as CTC-clusters, with greatly enhanced metastasis propensity.
2014-07-11 | GSE51827 | GEO
Project description:Tumor-derived circulating endothelial cell clusters in colorectal cancer
| PRJNA300264 | ENA
Project description:Molecular characterization of breast cancer circulating tumor cells (CTCs) associated with brain metastasis
| PRJNA388380 | ENA
Project description:Circulating Cancer-Associated Fibroblasts (cCAFs) have been discovered in circulating tumor cell clusters from all stages of disease progression in breast cancer patients. As the most abundant non-cancerous cell type in the tumor microenvironment (TME), CAFs impart many of the tumor promoting functions defined by the hallmarks of cancer such as: proliferation, invasion, migration, metastasis, stemness, immunosuppression, altered cancer cell metabolism, and drug resistance. Human primary CAF cell lines can form co-clusters in vitro with human breast cancer cells when grown in ultra-low attachment conditions. We have previously used these co-clusters to show that they promote metastasis in the mouse tail vein model. In this study, we seek to understand the cross-talk that occurs between CAFs and TNBC cells when they are present in heterotypic co-clusters compared to TNBC monoclusters or CAF monoclusters. We created samples of mono-clusters and co-clusters grown in 3D conditions for 48 hrs, then disrupted the clusters into a single cell suspension, and subsequently processed them for Single-cell RNA sequencing. Comparisons of breast cancer cells grown as mono-clusters versus co-clusters revealed differentially expressed genes (DEGs) that are up and down regulated in the presence of CAFs. Integration Pathway Analysis and Gene Ontology analysis revealed that CAFs increase expression of several components of the fibrinolysis pathway in breast cancer cells, such as uPA/PLAU and SERPINE1. Upstream regulators identified included TGFbeta. We also looked at DEGs in CAFs when in co-clusters versus mono-clusters and found that when in co-clusters, CAFs become even more CAF-like with the upregulation of genes such as collagens, integrins, and FN1. This study provided us with candidates to study in the process of CAF-mediated breast cancer cell extravasation, such as uPA/PLAU. Pathways identified support our conclusions that circulating CAFs are important players in the metastatic process.
2025-06-25 | GSE300584 | GEO
Project description:Gene expression profiling of circulating tumor cells in breast cancer
| PRJNA239696 | ENA
Project description:The presence of circulating tumor cell (CTC) clusters is associated with disease progression, new metastasis formation and reduced survival in a variety of cancer types. In breast cancer, pre-clinical studies showed that inhibitors of the Na+/K+-ATPase can suppress CTC clusters shedding and block metastasis. Here, we conducted a prospective, open-label, phase I study in patients with metastatic breast cancer, where the primary endpoint was to determine whether a short (one week) treatment with the Na+/K+-ATPase inhibitor digoxin could reduce mean CTC cluster size. Mechanistically, transcriptome profiling of CTCs highlighted downregulation of cell-cell adhesion and cell cycle-related genes upon treatment with digoxin, in line with its cluster-dissolution activity. ClinicalTrials.gov identifier: NCT03928210.
2024-12-06 | GSE249233 | GEO
Project description:Recent technological advances have made it possible to detect circulating breast cancer cells as precursors of distant metastasis and as prognosis marker in nonmetastatic breast cancer patients. Association of circulating tumor cells (CTCs) with molecular alteration in the primary tumor is not widely explored. We reported differential profile of altered genome, copy number alteration and copy-neutral loss of heterogeneity in 14 primary tumors when comparing patients with CTCs+ versus CTCs- using single-nucleotide polymorphism array. The most prevalent copy number alteration in CTCs+ patients was at 8q and particularly at the cytoband 8q24 (MYC loci). As the role of MYC in the process of tumor cell invasion and migration is controversial, we further validated in a larger series of patients whether altered MYC (amplification or gained) in primary tumors was correlated with the presence of CTCs in peripheral blood (as a surrogate of micrometastais). No correlation between MYC alteration and presence of CTCs was observed, providing clinical support to the recent data that MYC suppresses cancer metastasis or at least suggesting that MYC alteration could be contributory but insufficient for the generation of CTCs. This molecular association needs to be further characterized in preclinical model and especially clinically. We analyzed CN and LOH of CTC+ and CTC-
2014-11-19 | E-GEOD-43149 | biostudies-arrayexpress
Project description:<p>This study examines how altering systemic serine and glycine availability through dietary intervention affects breast cancer metastasis in vivo. Female NOD-SCID-gamma (NSG) mice were maintained on either a control amino acid–replete diet or a serine/glycine-enriched diet for two weeks before and during metastatic progression of human breast cancer cells. By integrating dietary manipulation with in vivo metastasis assays, this study tests whether changes in circulating and tissue nutrient levels can influence metastatic colonization and tumor growth across organs. These data provide insight into how nutrient availability shapes the metabolic environment and metastatic potential of cancer cells.</p>
2025-12-30 | MTBLS13151 | MetaboLights
Project description:Tumor microRNA expression profiling identifies circulating microRNAs for earlier breast cancer detection
| PRJNA253008 | ENA