The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Circulating Tumor Cell Clusters Are Oligoclonal Precursors of Breast Cancer Metastasis
Open accessAbstract
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. Using mouse models with tagged mammary tumors, we demonstrate that CTC-clusters arise from oligoclonal tumor cell groupings and not from intravascular aggregation events. Although rare in the circulation compared with single CTCs, CTC-clusters have 23-50-fold increased metastatic potential. In patients with breast cancer, single-cell resolution RNA sequencing of CTC-clusters and single CTCs, matched within individual blood samples, identifies the cell junction component plakoglobin as highly differentially expressed. In mouse models, knockdown of plakoglobin abrogates CTC-cluster formation and suppresses lung metastases. In breast cancer patients, both abundance of CTC-clusters and high tumor plakoglobin levels denote adverse outcomes. Thus, CTC-clusters are derived from multicellular groupings of primary tumor cells held together through plakoglobin-dependent intercellular adhesion, and while rare, they greatly contribute to the metastatic spread of cancer.
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Cites
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Cited by
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Inflammation and cancer: triggers, mechanisms, and consequences
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Metadata
- Authors
- Aceto, N., Bardia, A., Miyamoto, D. T., Donaldson, M. C., Wittner, B. S., Spencer, J. A., Yu, M., Pely, A., Engstrom, A., Zhu, H., Brannigan, B. W., Kapur, R., Stott, S. L., Shioda, T., Ramaswamy, S., Ting, D. T., Lin, C. P., Toner, M., Haber, D. A., & Maheswaran, S.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 158
- Issue
- 5
- Pages
- 1110-1122
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1993913242
- Cited by
- 2,441
- References
- 7
- FWCI
- 70.23
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Aceto, N., Bardia, A., Miyamoto, D. T., Donaldson, M. C., Wittner, B. S., Spencer, J. A., Yu, M., Pely, A., Engstrom, A., Zhu, H., Brannigan, B. W., Kapur, R., Stott, S. L., Shioda, T., Ramaswamy, S., Ting, D. T., Lin, C. P., Toner, M., Haber, D. A., & Maheswaran, S. (2014). Circulating Tumor Cell Clusters Are Oligoclonal Precursors of Breast Cancer Metastasis. Cell. https://doi.org/10.1016/j.cell.2014.07.013
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