Cancer Associated Fibroblasts: The Architects of Stroma Remodeling.

Fibroblasts have exceptional phenotypic plasticity and capability to secrete vast amount of soluble factors, extracellular matrix components and extracellular vesicles. While in physiological conditions this makes fibroblasts master regulators of tissue homeostasis and healing of injured tissues, in solid tumors cancer associated fibroblasts (CAFs) co-evolve with the disease, and alter the biochemical and physical structure of the tumor microenvironment, as well as the behavior of the surrounding stromal and cancer cells. Thus CAFs are fundamental regulators of tumor progression and influence response to therapeutic treatments. Increasing efforts are devoted to better understand the biology of CAFs to bring insights to develop complementary strategies to target this cell type in cancer. Here we highlight components of the tumor microenvironment that play key roles in cancer progression and invasion, and provide an extensive overview of past and emerging understanding of CAF biology as well as the contribution that MS-based proteomics has made to this field.