Clusters of circulating tumor cells traverse capillary-sized vessels

Area of Science:

• Oncology
• Biophysics
• Cell Biology

Background:

• Multicellular aggregates of circulating tumor cells (CTC clusters) are key drivers of distant organ metastasis.
• Current understanding assumes CTC clusters are too large to traverse narrow capillary vessels.

Purpose of the Study:

• To investigate the ability of CTC clusters to navigate microvascular constrictions.
• To challenge the assumption that CTC clusters cannot pass through narrow vessels.

Main Methods:

• Utilized microfluidic devices mimicking human capillary constrictions.
• Tested CTC clusters derived from patients and cancer cell lines in whole blood.
• Performed xenotransplantation of human CTC clusters into zebrafish for in vivo validation.

Main Results:

• Over 90% of CTC clusters (up to 20 cells) successfully traversed 5- to 10-μm constrictions.
• CTC clusters dynamically reorganized into single-file chains, reducing hydrodynamic resistance.
• In vivo studies in zebrafish confirmed similar cluster reorganization and capillary transit.

Conclusions:

• CTC clusters can navigate capillary-sized vessels by reversibly reorganizing their structure.
• This previously unrecognized capability suggests CTC clusters may significantly contribute to tumor dissemination.
• Potential therapeutic strategies targeting CTC cluster transit could combat metastasis.