BiCiCle · Biophysics of circulating tumor cells, from single molecule to cell clusters
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-09-01 → 2022-08-31
- EU contribution
- €164,946
- Participants
- 2
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Biophysics of circulating tumor cells, from single molecule to cell clusters
More than 90% of cancer-related deaths (more than eight million deaths worldwide each year) are due to the development of tumor metastasis, a complex process with multiple steps in which cancer cells spread within the patient’s body. There is an emerging realization that the fearsome transmitters of this cancer dissemination are clusters of so-called circulating tumor cells (CTC) that detach from the primary tumor, disseminate and home themselves in distant tissues. During their travel together in the bloodstream, they are subjected to important mechanical forces, for example, while passing through small capillaries. Nevertheless, the current knowledge of how these cells are held together is extremely limited. This project aims at unravelling the biophysical properties of CTCs clusters and its dynamic changes that enable clusters to pass through small capillaries. To better understand this, we offered to characterize the adhesion forces between cells and the viscoelastic properties of individual CTC and CTC clusters using an advanced technique called atomic force microscopy. However, this technique involves immobilizing the cells on a surface to perform the measurements, which does not correspond to the physiological state of circulating cells. We therefore sought to develop a new technique for measuring the mechanical properties of cells directly in suspension. To do so, we combined acoustic force spectroscopy, an emerging technique using sounds waves to manipulate or levitate micro-objects, and reflection contract interference microscopy, an optical technique known since decades. We have demonstrated that this unique combination allows measuring the deformation of objects in suspension.
Data: CORDIS, © European Union
Project objective
The major cause of cancer-associated mortality is tumor metastasis, a complex multistep process where cancer cells spread within the patient’s body. There is an emerging realization that the fearsome vectors of this cancer dissemination are clusters of so-called circulating tumor cells (CTC) that travel together in the bloodstream where they are subjected to important mechanical forces. Nevertheless, the current knowledge of how these cells are held together is extremely limited. This proposal aims at unravelling the biophysical properties of CTCs clusters from the molecular level to the multicellular level. The applicant Dr Valotteau proposes to use her experience in atomic force microscopy (AFM) to carry out this project under the supervision of Dr Rico who has well-established expertise in high speed force spectroscopy (HS-FS), in collaboration with Dr Pannequin who is a specialist of CTC. This project will be hosted by CNRS in the Laboratoire Adhesion & Inflammation (LAI) which is one of a very few laboratories worldwide equipped with HS-FS, enabling to correlate the characterization of the cell-cell adhesion with the study of the viscoelastic properties of single CTC and CTC clusters over a wide dynamic range physiologically relevant. By gathering complementary resources at the crossroad of cell biology, biophysics and nanotechnology, this BiCiCle project will fill an important knowledge gap about CTC cluster and greatly benefit to the career development of Dr Valotteau. Indeed, this fellowship will provide her a stimulating multidisciplinary environment and topic to set the basis of her own independent research project to become an academic researcher leading in the interdisciplinary field of biophysics.
Original text from CORDIS.
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Data: CORDIS, © European Union