Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis

Aceto, Nicola and Bardia, Aditya and Miyamoto, David T. and Donaldson, Maria C. and Wittner, Ben S. and Spencer, Joel A. and Yu, Min and Pely, Adam and Engstrom, Amanda and Zhu, Huili and Brannigan, Brian W. and Kapur, Ravi and Stott, Shannon L. and Shioda, Toshi and Ramaswamy, Sridhar and Ting, David T. and Lin, Charles P. and Toner, Mehmet and Haber, Daniel A. and Maheswaran, Shyamala. (2014) Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell, 158 (5). pp. 1110-1122.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/61356/

Downloads: Statistics Overview


Circulating tumor cell clusters (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- to 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 though rare, they greatly contribute to the metastatic spread of cancer.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cancer Metastasis (Aceto)
UniBasel Contributors:Aceto, Nicola
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cell Press
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:09 Dec 2020 16:36
Deposited On:09 Dec 2020 16:36

Repository Staff Only: item control page