Figure 2.

Experimental methods employed to analyze the effects of stiffness and solid stress on cancer and stromal cells in vitro. (A) Experimental setups studying the effect of ECM stiffness on cancer and stromal cells. There are two-dimensional models (2D) consisting of (i) a cell monolayer seeded on coating substrates (e.g., collagen type I or fibronectin) and three-dimensional models (3D) consisting of (ii) tumor spheroids or (iii) single cells embedded in a matrix (e.g., collagen type I, matrigel). Both models were aimed to investigate the effect of changes in extracellular rigidity on the transduction of mechanical signals into the cells as well as on the migration, invasion, proliferation and gene expression of cancer and stromal cells (B) Experimental setups studying the effect of solid stress on cancer and stromal cells. Setups include tumor spheroids that grow within (i) a polymer matrix, (ii) within elastic capsules, or (iii) in a confined polymer device. (iv,v) The setups are composed of cells seeded on the inner chamber of a transwell insert on the top of which an agarose cushion is placed or are embedded in a polymer matrix. A piston with adjustable weight applies a predefined and measurable compressive solid stress on the cells. These models provided useful information about the direct effect of solid stress on tumor growth and morphology as well as on cancer cell proliferation, migration, and gene expression. (C) A summary of in vitro and in vivo studies for the effect of solid stress in tumor progression.