Biomechanical and biochemical remodeling of stromal extracellular matrix in cancer

The extracellular matrix (ECM) provides structural and biochemical signals that regulate cell function. A well-controlled balance between cells and surroundings (i.e., dynamic reciprocity) is crucial for regulating ECM architecture. During cancer progression, epithelial cells undergo genetic alterations which, together with stromal changes including ECM remodeling, disturb the homeostatic dynamics of the epithelium. A parallel organization of stromal ECM fibrils is associated with tumorigenic responses. In an emerging paradigm, continuous and progressive regulation via mechanical forces and aberrant signaling are believed to be responsible for tumor-associated ECM remodeling. In this review we discuss the discrete biomechanical and biochemical mechanisms that underlie these architectural changes and highlight their particular relevance to the regulation of the alignment of ECM in the mesenchymal stroma.