Understanding and measuring mechanical signals in the tumor stroma.

The tumor microenvironment (TME) is well known for its immune suppressive role, especially in solid tumors which are characterized by a thick, dense stroma. Apart from cell-cell interactions and biochemical signals, the tumor stroma is also characterized by its distinct mechanical properties, which are dictated by the composition and architecture of its extracellular matrix (ECM). Cancer-associated fibroblasts (CAFs) are the main producers and remodelers of the stromal ECM, and their heterogeneity has recently become a focus of intense research. This review describes recent findings highlighting CAF subtypes and their specific functions, as well as the development of 3D models to study tumor stroma mechanics in vitro. Finally, we discuss the quantitative techniques used to measure tissue mechanical properties at different scales. Given the diagnostic and prognostic value of stroma stiffness and composition, and the recent development of anti-tumor therapeutic strategies targeting the stroma, understanding and measuring tumor stroma mechanical properties has never been more timely or relevant.