PUBLICATION
Clusters of circulating tumor cells traverse capillary-sized vessels
- Authors
- Au, S.H., Storey, B.D., Moore, J.C., Tang, Q., Chen, Y.L., Javaid, S., Sarioglu, A.F., Sullivan, R., Madden, M.W., O'Keefe, R., Haber, D.A., Maheswaran, S., Langenau, D.M., Stott, S.L., Toner, M.
- ID
- ZDB-PUB-160420-2
- Date
- 2016
- Source
- Proceedings of the National Academy of Sciences of the United States of America 113(18): 4947-52 (Journal)
- Registered Authors
- Langenau, David, Moore, John
- Keywords
- CTC clusters, cancer metastasis, capillary microhemodynamics, circulating tumor cell cluster microemboli, microfluidics
- MeSH Terms
-
- Capillaries/pathology*
- Cell Movement*
- Humans
- Neoplastic Cells, Circulating*
- PubMed
- 27091969 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Au, S.H., Storey, B.D., Moore, J.C., Tang, Q., Chen, Y.L., Javaid, S., Sarioglu, A.F., Sullivan, R., Madden, M.W., O'Keefe, R., Haber, D.A., Maheswaran, S., Langenau, D.M., Stott, S.L., Toner, M. (2016) Clusters of circulating tumor cells traverse capillary-sized vessels. Proceedings of the National Academy of Sciences of the United States of America. 113(18):4947-52.
Abstract
Multicellular aggregates of circulating tumor cells (CTC clusters) are potent initiators of distant organ metastasis. However, it is currently assumed that CTC clusters are too large to pass through narrow vessels to reach these organs. Here, we present evidence that challenges this assumption through the use of microfluidic devices designed to mimic human capillary constrictions and CTC clusters obtained from patient and cancer cell origins. Over 90% of clusters containing up to 20 cells successfully traversed 5- to 10-μm constrictions even in whole blood. Clusters rapidly and reversibly reorganized into single-file chain-like geometries that substantially reduced their hydrodynamic resistances. Xenotransplantation of human CTC clusters into zebrafish showed similar reorganization and transit through capillary-sized vessels in vivo. Preliminary experiments demonstrated that clusters could be disrupted during transit using drugs that affected cellular interaction energies. These findings suggest that CTC clusters may contribute a greater role to tumor dissemination than previously believed and may point to strategies for combating CTC cluster-initiated metastasis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping