It is unequivocal that ECM components are not only functionally diverse, being able to trigger a wide range of cellular activities, but also extremely dynamic, constantly undergoing remodeling processes wherein one or more of their essential properties are modified. Together with the reciprocal nature of cell–ECM interactions, it is evident that modulation of ECM dynamics is an effective strategy for cells to respond to environmental changes, adjust their behaviors accordingly, and maintain tissue integrity and function.
An important area of future research is to identify the diverse and novel roles of ECM components, especially with regard to its distinct physical, biochemical, and biomechanical properties, in various cellular and developmental processes. The fact that different ECM components can selectively bind to growth factors, which are often repeatedly used in multiple tissue compartments and at different times of organ development, and mediate directional signaling, has profound implications in understanding normal development and cancer. It is conceivable that deregulation of ECM dynamics may lead to a disruption of directional epithelial-mesenchymal cross talk, the basis of normal organ formation and homeostasis. Understanding the roles of ECM dynamics in the dialogues between different tissue components, therefore, can lead to a better understanding of the etiology of certain human congenital defects and cancers.
Considering the advances that have been made in the field of ECM biomechanics, an important next challenge will be to understand how different tissues establish and maintain their distinctive elasticity, and how normal tissue elasticity may be lost with age or under disease conditions. Abnormal ECM stiffness, as observed in tissue fibrosis, clearly plays an important role in cancer progression. It remains unclear, however, at the molecular level, how such abnormalities lead to changes in cell behavior and how different cell types may be affected.
Although the niche role has been well accepted in stem cell biology and has an increasing role in the cancer stem cell concept, and evidence supporting the ECM as an important and dynamic component of the niche is emerging, the mechanisms whereby ECM components function in stem cell biology still remain sketchy. What are the ECM components in the established invertebrate and vertebrate model systems? How do they interact with niche cells and paracrine signals and participate in the establishment and maintenance of stem cells? How does the niche ECM differ from non-niche ECM, and why does the former maintain stem cell properties, whereas the latter promotes differentiation? Clearly, a better understanding of the role of ECM biomechanics and dynamics in adult stem cell biology will have profound implications in the field of tissue engineering and regenerative medicine.