Université PSL

Cancer cell biomechanics under flow

Cancer cell biomechanics under flow
Understanding and fighting the metastatic process is a major challenge in the fight against cancer. It most often involves cells migrating from a primary tumor into the bloodstream, from where they reach a distant organ by extravasation. Once in the bloodstream, tumor cells experience shear stress and repeatedly encounter obstacles, e.g. narrow vessels in which they undergo mechanical deformation.

We showed that cancer cell lines flown in microfluidic systems mimicking the blood circulation may undergo DNA damage and modify their expression of mechanosensitive pathways.

The central hypothesis of this project is thus that the circulation has in itself a significant impact on various facets of circulating tumor cells (CTCs) physiology and fate, and consequently on the metastatic process as a whole. This project gathers physicists, biologists and clinicians to develop the potential of this hypothesis in oncology.

We shall first explore the role of pathways previously identified as being affected in cells under static or quasistatic confinement, associated e.g. with nuclear membrane tension and rupture (leading to DNA damage), or volume regulation at the whole cell level (targeting cell survival). This exploration will use state-of-the-art cell biology methods, e.g. live imaging, pharmacology or KO of specific genes. In parallel, we will implement a general transcriptomic approach to identify pathways specifically affected by the circulation stimuli. We shall first use cell lines, including CTC lines established in this consortium, then primary cells from patients “naïve” to circulation (ascites).

We expect to identify this way i:druggable targets likely to reduce the resistance of CTCs to the repetitive mechanical deformations induced by the blood circulation, or to limit the induction of aggressive phenotypes, and/or ii: new markers/signatures of the survival and dissemination potential of cancer cells in circulation, for treatment orientation.

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Macromolécules and Microsystems in Biology and Medecine Team

Systemic Cellular Biology of Polarity and Division Team

Illustration: Schematic representation and superimposition of images showing a tumor cell transiting in a microfluidic channel mimicking the blood circulation.
Cognart, H. A., Viovy, J. L., & Villard, C. (2020). fluid shear stress coupled with narrow constrictions induce cell type-dependent morphological and molecular changes in SK-BR-3 and MDA-MB-231 cells. Scientific reports, 10(1), 1-14.