Deciphering the "Collagen code" in tumor progression

Invasion and metastasis are the fundamental properties of tumor biology and the root causes of cancer death. With the elucidation of genetic and epigenetic mechanisms, it has been postulated that cancer is a disease of imbalance. It is not merely a disease of tumor cells but also the body's mismanagement of those tumor cells. Tumor microenvironment plays an important role in tumor progression via the co-evolution of tumor cells and tumor stroma. Hence, exploring the complex mechanisms of tumor progression from perspectives of tumor stroma has become a new frontier. The major component of tumor stroma, the extracellular matrix (ECM), acts as a key regulator of cell and tissue function. Conventionally, the role of ECM was considered primarily as a physical scaffold that binds cells and tissues together. However, recent studies revealed the biochemical and biophysical signaling properties of the ECM as well that affect cell adhesion and migration, tissue morphogenesis and repair, and angiogenesis and cancer. The most abundant constituent of ECM, collagen, accounts for the major function of ECM, which can be associated with increased malignancy. The present review summarizes the dynamic interplay between collagen and tumor cells. It focuses on changes in physicochemical-biological properties of collagen. A new paradigm has been formulated that collagen can no more be considered playing a passive role over which tumor progression and metastasis takes place. Rather, its active role in the promotion of tumor progression and metastasis should be explored.