Collection of Blood Specimens for Circulating Tumor Cell Analysis
Ontology highlight
ABSTRACT:
DISEASE(S): Prostatic Neoplasms,Neoplastic Cells, Circulating,Colorectal Cancer,Colorectal Neoplasms,Prostate Cancer,Breast Cancer
PROVIDER: 2151681 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Circulating tumour cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. While these cells are extraordinarily rare, they may identify cellular pathways contributing to the blood-borne dissemination of cancer. Here, we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to single-molecule RNA sequencing, identifying Wnt2 as enriched in CTCs. Expression of Wnt2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. The effect of Wnt2 is correlated with fibronectin upregulation, and it is mediated in part through non-canonical Wnt signaling and suppressed by inhibition of the Map3k7 (Tak1) kinase, an integrator of Wnt, BMP and TGF-beta signaling. In humans, formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple Wnt genes, and pancreatic CTCs revealed significant enrichment for non-canonical Wnt signaling in 5 of 11 cases. Thus, molecular analysis of CTCs may identify novel therapeutic targets to prevent the distal spread of cancer. Expression profiling of circulating tumor cells in human pancreatic cancer patients support a hypothesis that WNT signaling plays a role in pancreatic cancer metastasis.
2012-08-17 | E-GEOD-40174 | biostudies-arrayexpress
Project description:Circulating tumour cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. While these cells are extraordinarily rare, they may identify cellular pathways contributing to the blood-borne dissemination of cancer. Here, we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to single-molecule RNA sequencing, identifying Wnt2 as enriched in CTCs. Expression of Wnt2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. The effect of Wnt2 is correlated with fibronectin upregulation, and it is mediated in part through non-canonical Wnt signaling and suppressed by inhibition of the Map3k7 (Tak1) kinase, an integrator of Wnt, BMP and TGF-beta signaling. In humans, formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple Wnt genes, and pancreatic CTCs revealed significant enrichment for non-canonical Wnt signaling in 5 of 11 cases. Thus, molecular analysis of CTCs may identify novel therapeutic targets to prevent the distal spread of cancer. Expression profiling of primary tumor, circulating tumor cells and ascites in a mouse model of pancreatic cancer suggested WNT signaling plays a role in pancreatic cancer metastasis. Induction of Wnt2 signaling in mouse pancreatic NB508 cells supported the hypothesis.
2012-08-17 | E-GEOD-40171 | biostudies-arrayexpress
Project description:Circulating Tumor Cells (CTCs) are shed from primary tumors into the bloodstream, mediating the hematogenous spread of cancer to distant organs. Using a pancreatic cancer mouse model, we applied a microfluidic device to isolate CTCs independently of tumor epitopes, subjecting these to single cell RNA-sequencing. This study was conducted to determine the heterogeneity of pancreatic CTCs and to compare these CTCs to matched primary tumors, cell line controls (NB508 cancer cell line and MEF non-cancer cell line), primary tumor single cells, and normal leukocytes/WBCs. We profiled RNA from 75 single cells circulating in mouse blood enriched for circulating tumor cells from 5 mice, 12 single cells from a mouse embryonic fibroblast cell line, 16 single cells from the nb508 mouse pancreatic cancer cell line, 12 single mouse white blood cells, 18 single GFP lineage-traced circulating tumor cells from two mice, 20 single GFP lineage-traced cancer cells from the primary pancreatic tumor of a mouse, and 34 dilutions to 10 or 100 picograms of total RNA from mouse primary pancreatic tumors from 4 mice.
2014-09-22 | E-GEOD-51372 | biostudies-arrayexpress
Project description:Circulating tumour cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. While these cells are extraordinarily rare, they may identify cellular pathways contributing to the blood-borne dissemination of cancer. Here, we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to single-molecule RNA sequencing, identifying Wnt2 as enriched in CTCs. Expression of Wnt2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. The effect of Wnt2 is correlated with fibronectin upregulation, and it is mediated in part through non-canonical Wnt signaling and suppressed by inhibition of the Map3k7 (Tak1) kinase, an integrator of Wnt, BMP and TGF-beta signaling. In humans, formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple Wnt genes, and pancreatic CTCs revealed significant enrichment for non-canonical Wnt signaling in 5 of 11 cases. Thus, molecular analysis of CTCs may identify novel therapeutic targets to prevent the distal spread of cancer.
2012-08-17 | GSE40174 | GEO
Project description:Circulating tumour cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. While these cells are extraordinarily rare, they may identify cellular pathways contributing to the blood-borne dissemination of cancer. Here, we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to single-molecule RNA sequencing, identifying Wnt2 as enriched in CTCs. Expression of Wnt2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. The effect of Wnt2 is correlated with fibronectin upregulation, and it is mediated in part through non-canonical Wnt signaling and suppressed by inhibition of the Map3k7 (Tak1) kinase, an integrator of Wnt, BMP and TGF-beta signaling. In humans, formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple Wnt genes, and pancreatic CTCs revealed significant enrichment for non-canonical Wnt signaling in 5 of 11 cases. Thus, molecular analysis of CTCs may identify novel therapeutic targets to prevent the distal spread of cancer.
2012-08-17 | GSE40171 | GEO
Project description:Circulating Tumor Cells (CTCs) are shed from primary tumors into the bloodstream, mediating the hematogenous spread of cancer to distant organs. Using a pancreatic cancer mouse model, we applied a microfluidic device to isolate CTCs independently of tumor epitopes, subjecting these to single cell RNA-sequencing. This study was conducted to determine the heterogeneity of pancreatic CTCs and to compare these CTCs to matched primary tumors, cell line controls (NB508 cancer cell line and MEF non-cancer cell line), primary tumor single cells, and normal leukocytes/WBCs.
2014-09-22 | GSE51372 | GEO
Project description:This pilot study will aim to determine whether circulating tumor cells (CTCs) can be captured using the novel cMET based ferrofluid. The primary objective of this pilot study will be to describe the numbers of c-MET expressing cells that can be detected by the c-MET CTC capture technique. These data will be separated by disease site. The investigator will also describe the detection rates of both the c-MET CTC capture and the EpCAM CTC capture techniques in each patient, also separated by disease site.
| 2162178 | ecrin-mdr-crc
Project description:By applying RNA-ISH and RNAseq to circulating tumor cells (CTCs), the study provides definitive evidence of epithelial to mesenchymal transition (EMT) across all histological types of breast cancer, identifying mediators such as FOXC1 and TGF-β signaling, and demonstrating dynamic treatment-associated changes in EMT within clusters of CTCs. Epithelial to mesenchymal transition (EMT) has been postulated to contribute to the migration and dissemination of cancer cells, but supporting histopathological evidence is limited. We used a microfluidic device to isolate circulating tumor cells (CTCs), combined with multiplex fluorescent RNA-in-situ hybridization (ISH) and RNA sequencing, to quantify and characterize EMT in breast cancer cells within the bloodstream. Whereas only rare (0.1-10%) cells in the primary tumor expressed both mesenchymal and epithelial markers, such biphenotypic as well as purely mesenchymal cells were enriched among CTCs, across all histological subtypes of breast cancer. In an index patient followed longitudinally, fluctuation in epithelial and mesenchymal states was observed as a function of initial response and subsequent resistance to therapy. Mesenchymal markers were predominant in clusters of tumor cells, many of which had adherent platelets. Finally, RNA sequencing of CTC clusters identified TGF-β and other EMT-related signatures, which were absent from more epithelial CTCs. FOXC1, a known regulator of EMT, was abundantly expressed in mesenchymal CTCs and was detectable within localized regions of the primary breast tumor. Together, these data support a role for EMT in the blood-borne dissemination of breast cancer and point to the dynamic nature of this cell fate change.
2013-02-01 | E-GEOD-41245 | biostudies-arrayexpress
Project description:Melanoma is an invasive malignancy with a high frequency of blood-borne metastases, but circulating tumor cells (CTCs) have not been readily isolated. We adapted microfluidic CTC capture to a tamoxifen-driven B-RAF/PTEN mouse melanoma model. CTCs were detected in all tumor-bearing mice, rapidly declining after B-RAF inhibitor treatment. CTCs were shed early from localized tumors and a short course of B-RAF inhibition following surgical resection was sufficient to dramatically suppress distant metastases. The large number of CTCs in melanoma-bearing mice enabled comparison of RNA sequencing profiles with the matched primary tumor. A mouse melanoma CTC-derived signature correlated with invasiveness and cellular motility in human melanoma. In patients with metastatic melanoma, CTCs were detected in smaller numbers in patients with metastatic melanoma and declined with successful B-RAF targeted therapy. Together, the capture of CTCs and their molecular characterization provide insight into the hematogenous spread of melanoma.
2014-03-31 | GSE52031 | GEO
Project description:Cancer cells metastasize through the bloodstream either as single migratory circulating tumor cells (CTCs) or as multicellular groupings (CTC-clusters). Existing technologies for CTC enrichment are designed primarily to isolate single CTCs, and while CTC-clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here, we developed a microchip technology (Cluster-Chip) specifically designed to capture CTC-clusters independent of tumor-specific markers from unprocessed blood. CTC-clusters are isolated through specialized bifurcating traps under low shear-stress conditions that preserve their integrity and even two-cell clusters are captured efficiently. Highly parallel architecture of the chip allows deterministic screening of clinically relevant volumes of blood samples at slow, and hence, non-damaging flow rates. Using the Cluster-Chip, we identify CTC-clusters in 30-40% of patients with metastatic cancers of the breast, prostate and melanoma. RNA sequencing of CTC-clusters confirms their tumor origin and identifies leukocytes within the clusters as being tissue-derived macrophages. Together, the development of a device for efficient capture of CTC-clusters will enable detailed characterization of their biological properties and role in cancer metastasis.
2015-05-17 | GSE67939 | GEO