Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters.

ABSTRACT: Recent genomic studies challenge the conventional model that each metastasis must arise from a single tumor cell and instead reveal that metastases can be composed of multiple genetically distinct clones. These intriguing observations raise the question: How do polyclonal metastases emerge from the primary tumor? In this study, we used multicolor lineage tracing to demonstrate that polyclonal seeding by cell clusters is a frequent mechanism in a common mouse model of breast cancer, accounting for >90% of metastases. We directly observed multicolored tumor cell clusters across major stages of metastasis, including collective invasion, local dissemination, intravascular emboli, circulating tumor cell clusters, and micrometastases. Experimentally aggregating tumor cells into clusters induced

SUBMITTER: Cheung KJ 

PROVIDER: S-EPMC4763783 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature