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| Status |
Public on Jul 11, 2014 |
| Title |
Circulating Tumor Cell Clusters are Oligoclonal Precursors of Breast Cancer Metastasis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
RNA-seq from 29 samples (15 pools of single CTCs and 14 CTC-clusters) isolated from 10 breast cancer patients
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| Contributor(s) |
Aceto N, Bardia A, Spencer JA, Wittner BS, Yu M, Donaldson MC, Pely A, Engstrom A, Zhu H, Brannigan BW, Kapur R, Stott SL, Shioda T, Ramaswamy S, Ting DT, Lin CP, Toner M, Haber DA, Maheswaran S |
| Citation(s) |
25013076, 25171411 |
| Submission date |
Oct 29, 2013 |
| Last update date |
Jan 29, 2020 |
| Contact name |
Ben S. Wittner |
| E-mail(s) |
wittner.ben@mgh.harvard.edu
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| Organization name |
Massachusetts General Hospital
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| Department |
Center for Cancer Research
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| Lab |
Lawrence
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| Street address |
149 13th Street
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02129 |
| Country |
USA |
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| Platforms (1) |
| GPL16288 |
AB 5500xl Genetic Analyzer (Homo sapiens) |
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| Samples (29)
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| Relations |
| BioProject |
PRJNA225522 |
| SRA |
SRP032343 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE51827_platform.xls.gz |
1.4 Mb |
(ftp)(http) |
XLS |
| GSE51827_readCounts.xls.gz |
762.4 Kb |
(ftp)(http) |
XLS |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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