Thèses

Vendredi 7 Juillet 2023 à 14h00.

Long-term regulation of colorectal cancer cells under mechanical stress

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Directeur de thèse / thesis director : Charlotte Rivière et Sylvain Monnier

Membres du jury / jury members :

Dr. Claire WILHELM
Pr. Sylvain GABRIELE
Dr. Emmanuèle HELFER
Dr. Véronique MAGUER-SATTA
Dr. Olivier MEURETTE
Dr. Giovanni CAPPELLO
Dr. Charlotte RIVIERE
Dr. Sylvain MONNIER

Résumé / Abstract :

How cancer cells interact with their environment in situ has major implications for understanding tumor pathophysiology and response to therapy. Indeed, the tumor microenvironment strongly influences the tumor fate and more particularly a specific subpopulation of tumor cells that are recovering properties of stem cells, called cancer stem-like cells, which are extremely plastic. These cells are assumed to be largely responsible for tumor progression, treatment resistance and relapse. However, during tumor progression, the physical properties of the tumor microenvironment are also strongly modified compared to the surrounding healthy tissue. Therefore, cancer cells undergo major variations in the physical forces they withstand, including rigidification of the extracellular matrix and proliferation in a confined space. Thus, it is important to understand how this environment impacts them to better target therapeutic strategies. To disentangle the many factors that influence the structure, mechanics and function of tumor tissues and cells, our team has developed numerous hydrogel-based microsystems to reproduce in a standardized way the mechanical environment that the tumor undergoes in vivo. It is within this framework that my research project aims at understanding how the tumor environment, from a mechanical point of view, influences the long-term cancer cell fate. To do so, I combine two complementary approaches: mechanical deformation is imposed either in 2D by confining isolated cancer cells, or in 3D by isotropically compressing tumor spheroids.

Keywords: colorectal cancer; cancer mechanobiology; microenvironment; hydrogel microsystem; cancer stem cells; long-term regulation.

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