Biomatrices that mimic the cancer extracellular environment

The tumor microenvironment (TME), in particular the extracellular matrix (ECM), has been increasingly linked to the tumor aggressiveness and invasion. The dynamic interplay between cells and ECM regulates the normal function of tissues, modulating the cellular behavior and activating signaling events, mainly is triggered by the well-structured and organized components of the ECM. In cancer, the changes on the ECM composition derived from the deregulation of production and degradation of its constituents, alters the biochemical (e.g., upregulation of metalloproteinases and deposition of proteins) and mechanical (cross-linking extension of the matrix) features of the extracellular space, changing the normal function of tissues. From this perspective, the engineering of three-dimensional (3D) models that mimic the TME, allowing the in vitro study of cancer cells behavior, has emerged. These 3D models have been used to screen the role of the ECM components, such as proteins and glycans on cancer cells’ behavior. Moreover, the development of 3D TME models allows the recreation of the ECM by tuning its porosity and density, enabling the exchanges of nutrients, oxygen, and biochemical factors, which are essential for cell adhesion, proliferation, and migration. In the following chapter the natural-based materials used for the construction of these 3D models, such as collagen, hyaluronic acid, fibronectin, or laminin, components of the ECM, alginate, and chitosan will be reviewed. In addition, the use of synthetic-based materials such polyethylene glycol, poly(lactic acid), or polylactide-co-glycolide, that have been widely used in the development of 3D cancer models due to their biocompatibility and the ability to easily tune its physical properties, will be also briefly reviewed.