Le FORUM, Vol. 37 No. 1

https://digitalcommons.library.umaine.edu/francoamericain_forum/1036/thumbnail.jp

Magnetic Compression of Tumor Spheroids Increases Cell Proliferation In Vitro and Cancer Progression In Vivo

International audienceA growing tumor is submitted to ever-evolving mechanical stress. Endoscopic procedures add additional constraints. However, the impact of mechanical forces on cancer progression is still debated. Herein, a set of magnetic methods is proposed to form tumor spheroids and to subject them to remote deformation, mimicking stent-imposed compression. Upon application of a permanent magnet, the magnetic tumor spheroids (formed from colon cancer cells or from glioblastoma cells) are compressed by 50% of their initial diameters. Such significant deformation triggers an increase in the spheroid proliferation for both cell lines, correlated with an increase in the number of proliferating cells toward its center and associated with an overexpression of the matrix metalloproteinase−9 (MMP−9). In vivo peritoneal injection of the spheroids made from colon cancer cells confirmed the increased aggressiveness of the compressed spheroids, with almost a doubling of the peritoneal cancer index (PCI), as compared with non-stimulated spheroids. Moreover, liver metastasis of labeled cells was observed only in animals grafted with stimulated spheroids. Altogether, these results demonstrate that a large compression of tumor spheroids enhances cancer proliferation and metastatic process and could have implications in clinical procedures where tumor compression plays a role

Surface tension of model tissues during malignant transformation and epithelial–mesenchymal transition

International audienceEpithelial–mesenchymal transition is associated with migration, invasion, and metastasis. The translation at the tissue scale of these changes has not yet been enlightened while being essential in the understanding of tumor progression. Thus, biophysical tools dedicated to measurements on model tumor systems are needed to reveal the impact of epithelial–mesenchymal transition at the collective cell scale. Herein, using an original biophysical approach based on magnetic nanoparticle insertion inside cells, we formed and flattened multicellular aggregates to explore the consequences of the loss of the metastasis suppressor NME1 on the mechanical properties at the tissue scale. Multicellular spheroids behave as viscoelastic fluids, and their equilibrium shape is driven by surface tension as measured by their deformation upon magnetic field application. In a model of breast tumor cells genetically modified for NME1, we correlated tumor invasion, migration, and adhesion modifications with shape maintenance properties by measuring surface tension and exploring both invasive and migratory potential as well as adhesion characteristics