Figure 2.
Pressure and stiffness induced tumorigenesis in vivo. (a) Physical mimicking of pressure from hyperproliferative tumor growth in vivo is achieved by injection of ultramagnetic liposomes in the presence of small strong magnets subcutaneously localized in front of the colon that favor liposome extravasation and endocytosis into the mesenchymal cells that constitute the conjunctive tissue of colonic crypts epithelial cells, which generates the 1-kPa mouse tumor-growth pressure, leading to activation of the β-cat tumorigenic pathway through Y654–β-cat and Ser9-GSK3β phosphorylation in healthy epithelial cells tissue (Fernández-Sánchez et al., 2015). Ultramagnetic liposomes (red) colocalize with the intracellular Vimentin of mesenchymal cells (green), leading to the cytoplasmic orange–yellow labeling that surrounds the cell nuclei labeled with Dapi in blue. (b) Mimicking an increase in fibrotic stiffness in vivo is achieved by transgenic Rock activation in the epidermis. This results in activation of Myosin activity (pMypt1 staining), the increase of stiffness measured by AFM, and the inactivation of GSK3 by Ser9 phosphorylation leading to the tumorigenic β-cat pathway enhancement (Samuel et al., 2011).