Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis.
Cell
; 158(5): 1110-1122, 2014 Aug 28.
Article
em En
| MEDLINE
| ID: mdl-25171411
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Células Neoplásicas Circulantes
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Metástase Neoplásica
Limite:
Animals
/
Female
/
Humans
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Male
Idioma:
En
Revista:
Cell
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos