Physico-mechanical aspects of extracellular matrix influences on tumorigenic behaviors

Abstract

Tumor progression in vitro has traditionally been studied in the context of two-dimensional (2D) environments. However, it is now well accepted that 2D substrates are unnaturally rigid compared to the physiological substrate known as extracellular matrix (ECM) that is in direct contact with both normal and tumorigenic cells in vivo. Hence, the patterns of interactions, as well as the strategies used by cells in order to penetrate the ECM, and migrate through a three-dimensional (3D) environment are notoriously different than those observed in 2D. Several substrates, such as collagen I, laminin, or complex mixtures of ECM components have been used as surrogates of native 3D ECM to more accurately study cancer cell behaviors. In addition, 3D matrices developed from normal or tumor-associated fibroblasts have been produced to recapitulate the mesenchymal 3D environment that assorted cells encounter in vivo. Some of these substrates are being used to evaluate physico-mechanical effects on tumor cell behavior. Physiological 3D ECMs exhibit a wide range of rigidities amongst different tissues while the degree of stromal stiffness is known to change during tumorigenesis. In this review we describe some of the physico-mechanical characteristics of tumor-associated ECMs believed to play important roles in regulating epithelial tumorigenic behaviors.

Figure 1

Composite describing how tumorigenesis and mesenchymal stroma progression are two processes which affect and incite each other. The photographs represent confocal 3D reconstructions of fibroblast-derived ECMs (in brown) and cell nuclei (in green) where the disorganized in vitro stroma is shown in the left panel while the parallel patterned architecture of tumor-associated stromal matrix is evident in the right panel. The gradient progression bar in brown, at the bottom of the composite, represents the increased stiffness and architectural patterning of the stroma during these joint progression processes. The two confocal images are a variation from images published in Amatangelo, Bassi et al. 2005 [20].