Figure 1.

Schematic view of the roles of Col-I in cell invasion in TME. The middle row describes the type I collagen (Col-I) multiple forms. The (top row,bottom row) indicate the roles of Col-I in cancer cell invasion in tumor microenvironment (TME) and Col-I-influenced cell behaviors, respectively. Col-I molecules form supramolecular aggregates such as fibrils and fibers, or conversely, it forms gelatin upon denaturation. Gelatin is further degraded to peptides, which act as soluble factors (middle row). These variations in the Col-I form have distinct effects on cell behavior. In general, Col-I in the supramolecular aggregation state suppresses cell proliferation and migration, thereby inhibiting the malignant transformation of cancer, whereas Col-I molecules promote proliferation and migration, thereby promoting malignant transformation. In both conditions, EMT is induced (bottom row). It is said that Col-I, in its supramolecular aggregation state, exhibits contradictory functions: one is to act as a physical barrier against cancer and inflammatory cells, whereas the other is to provide a solid scaffold that promotes cancer cell invasion. Col-I peptides can act as chemotactic agents and may promote malignant transformation (top row).