Through the Eye of a Needle: Can Cancer Cell Clusters Transit through Capillaries?
Mechanical and Aerospace Engineering
Department Seminar Series
Sam H. Au, PhD
Massachusetts General Hospital and Harvard Medical School
Multicellular aggregates of circulating tumor cells in the bloodstream (CTC-clusters) are potent initiators of distant organ metastasis. However, it is currently believed that CTC-clusters, which sometimes contain up to 100 cells, are unable to disseminate to distant organs because their size prevents passage through vessels as narrow at 5 microns.
We challenged this assumption using microfluidic devices designed to mimic human capillaries. Over 90% of clusters containing up to 20 cells successfully traversed constrictions even in whole blood. Clusters reversibly reorganized into single-file chain-like geometries. Hydrodynamic analysis using custom Matlab® scripts demonstrated that this behavior substantially reduced their resistances to flow. Xenotransplantation of human CTC-clusters into zebrafish showed similar reorganization and transit through capillary-sized vessels in vivo. These findings suggest that CTC-clusters contribute a greater role to the dissemination of cancer than previously believed and may lead to strategies for combating CTC-cluster initiated metastasis.
Sam Au is a postdoctoral fellow at Massachusetts General Hospital and Harvard Medical working with Professor Mehmet Toner on microfluidic devices to study circulating tumor cell behavior within capillaries. He received his doctorate in Biomedical Engineering at the University of Toronto under Professor Aaron Wheeler, where he developed digital microfluidic devices for cellular applications. Sam is currently interested in better understanding the mechanical and biochemical cues which direct cancer cells within the vasculature into dramatically different fates.