Functional Interplay Between Collagen Network and Cell Behavior Within Tumor Microenvironment in Colorectal Cancer

Colorectal cancer is the second most common cancer diagnosed in men and the third most commonly occurring in women worldwide. Interactions between cells and the surrounding extracellular matrix (ECM) are involved in tumors development and progression of many types of cancer. The organization of the ECM molecules provides not only physical scaffoldings and dynamic network into which cells are embedded but also allows the control of many cellular behaviors including proliferation, migration, differentiation and survival leading to homeostasis, and morphogenesis regulation. Modifications of ECM composition and mechanical properties during carcinogenesis are critical for tumor initiation and progression. The core matrisome is constituted of three classes of macromolecules which are collagens, extracellular matrix glycoproteins and proteoglyans. In most tissues, fibrillar collagen is the major component of ECM. Cells embedded into fibrillar collagen interact with it through their surface receptors, such as integrins and discoidin domain receptors. On the one hand, cells incorporate signals from ECM that modify their functionalities and behaviors. On the other hand, all cells within tumor environment (cancer cells, cancer-associated fibroblasts, endothelial cells, immune cells) synthesize and secrete matrix macromolecules under the control of multiple extracellular signals. This cell-ECM dialog participates in a dynamic way in ECM formation and its biophysical and biochemical properties. In the present review we will discuss recent advances illustrating the functional interplay between cells and collagen network within the tumor microenvironment during colorectal cancer progression.