Cancer mortality mainly arises from metastases, due to cells that escape from a primary tumor, circulate in the blood as circulating tumor cells (CTCs), leave blood vessels and nest in distant organs. It is still unclear how CTCs overcome the harsh conditions of fluid shear stress and mechanical constraints within the microcirculation. A model of the blood microcirculation was established through the fabrication of microfluidic channels comprising constrictions. Metastatic breast cancer cells of epithelial-like and mesenchymal-like states were flowed into the microfluidic device. These cells were circulated, visualized while in circulation, and analyzed for their dynamical behavior. They were also retrieved post-circulation for staining of DNA damage response and gene expression analysis of key regulators of epithelial-to-mesenchymal transition. Altogether, changes from molecular to cellular scales were observed. Therefore, it is pivotal to consider the full consequences of the circulation in order to understand the metastatic cascade as a whole.
Blood Flow Dynamics Has a Major Influence on the State of Circulating Tumor Cells
Hamizah A. Cognart,J. Viovy,C. Villard
Published 2019 in bioRxiv
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- Publication year
2019
- Venue
bioRxiv
- Publication date
2019-08-06
- Fields of study
Medicine, Chemistry, Engineering
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