High blood flow shear stress values are associated with circulating tumor cells cluster disaggregation in a multi-channel microfluidic device

PLoS One. 2021 Jan 14;16(1):e0245536. doi: 10.1371/journal.pone.0245536. eCollection 2021.


Metastasis represents a dynamic succession of events involving tumor cells which disseminate through the organism via the bloodstream. Circulating tumor cells (CTCs) can flow the bloodstream as single cells or as multicellular aggregates (clusters), which present a different potential to metastasize. The effects of the bloodstream-related physical constraints, such as hemodynamic wall shear stress (WSS), on CTC clusters are still unclear. Therefore, we developed, upon theoretical and CFD modeling, a new multichannel microfluidic device able to simultaneously reproduce different WSS characterizing the human circulatory system, where to analyze the correlation between SS and CTC clusters behavior. Three physiological WSS levels (i.e. 2, 5, 20 dyn/cm2) were generated, reproducing values typical of capillaries, veins and arteries. As first validation, triple-negative breast cancer cells (MDA-MB-231) were injected as single CTCs showing that higher values of WSS are correlated with a decreased viability. Next, the SS-mediated disaggregation of CTC clusters was computationally investigated in a vessels-mimicking domain. Finally, CTC clusters were injected within the three different circuits and subjected to the three different WSS, revealing that increasing WSS levels are associated with a raising clusters disaggregation after 6 hours of circulation. These results suggest that our device may represent a valid in vitro tool to carry out systematic studies on the biological significance of blood flow mechanical forces and eventually to promote new strategies for anticancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomechanical Phenomena
  • Cell Line, Tumor
  • Cell Survival
  • Hemodynamics*
  • Humans
  • Lab-On-A-Chip Devices*
  • Models, Biological
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating / pathology*
  • Shear Strength*
  • Single-Cell Analysis
  • Stress, Mechanical*

Grants and funding

This work was supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 801159.