Characterization of clustered CTCs to eliminate breast cancer metastasis

Metastasis accounts for 90% of breast cancer deaths. Circulating tumor cells (CTCs) with stem cell properties are considered the seeds of distant metastasis. Compared to single CTCs, clusters of multiple CTCs possess 50 times higher metastatic capacity, contribute to polyclonal metastasis, and correlate with worse prognosis. However, the mechanisms how CTC clusters are generated are unclear. While it has been suggested that CTC clusters shed together from the primary tumor, our data suggest a different mechanism. Individual breast cancer cells, especially breast cancer stem cells (CSCs), are capable of following each other in a manner of linear stream migration and form aggregates in the vascular structure. This proposal hypothesizes that CSC properties contribute to CTC clustering and CTC polyclonal colonization occurs in a platelet-assisted manner. Anti-CSC therapeutic approaches will be explored to block CTC clustering and metastasis.