Blanc SVSE 5 - Blanc - SVSE 5 - Physique, chimie du vivant et innovations biotechnologiques

Tumor and environment : the role of mechanical stress in cancer invasion – Invaders

Submission summary

The INVADERS project aims to determine the effect of a Mechanical Stress on Cancer Invasion.

The current hypotheses favor either bi-directional biochemical signals between the tumor and the surrounding stroma or an integrated biomechanical competition between tumor and stroma. During the project INVADERS, we propose to design in vitro tumor/microenvironment models that allow us to decouple the biochemical and the biomechanical effects.

We will use a quantitative biophysics approach to understand the origin of compressive stresses in tumors, to determine whether these stresses may trigger cell escape from the tumor to the adjacent tissues and to investigate the role of different mechanical parameters, such as compression, confinement and local stiffness around the tumor.

In the project INVADERS, we propose:

1) To design the Biological Model suitable for in-vitro Invasion Assay under stress. This implies the choice cell lines and the elaboration of a unique protocol to produce a large number of identical and monoclonal multicellular spheroids.

2) To set the in vitro Invasion Assay, based on multicellular spheroids embedded in a reconstituted Simplified Stroma.
The Simplified Stroma will be made of:
i. a Layer of Matrigel, to mimic the Basement Membrane that surrounds tumors,
ii. a Shell of Alginate, to impose the mechanical constraint and
iii. a Collagen Matrix, through which the invasive cells will migrate. The migration through the collagen gel will be the read-out for the invasive phenotype.

3) To determine the impact of the mechanical stress on cancer invasion through a series of Invasion Assays, in which tumors grow either at constant stiffness/volume or at constant mechano-osmotic pressure.

Project coordination

Giovanni CAPPELLO (Laboratoire Interdisciplinaire de Physique)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

LIPhy Laboratoire Interdisciplinaire de Physique
IOGS (Institut d'Optique Théorique et Appliquée) Laboratoire Photonique Numérique, Nanosciences
IC Institut Curie

Help of the ANR 479,783 euros
Beginning and duration of the scientific project: October 2013 - 36 Months

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