Laminins and matrix metalloproteinases connection: a subtle relationship that can go wrong in a tumor context, particularly if CD44 gets involved

Laminins (LM) are large extracellular glycoproteins involved in several biological processes, including cellular interactions, self-polymerization, and binding with other extracellular matrix proteins. LMs influence cell function by inducing various signaling pathways via cell membrane receptors and have multiple, often cell type-specific, functions in, for example, adhesion, differentiation, migration, and phenotype maintenance, and they also provide resistance to apoptosis. They are also important components of basement membranes. The basement membrane is partly degraded in the course of tumor growth, facilitating the invasion of budding cells and their migration to lymphatic or blood vessels. In this context, LMs undergo proteolytic cleavage, which disrupts their involvement in maintaining the structural and biological properties of the basement membrane. LMs are also involved via their participation in cancer cell adhesion and migration processes. These events are either supported by their major cell binding domains or triggered by cryptic interaction sites revealed by matrix metalloproteinase (MMP)-induced proteolytic cleavage. While being ideal targets for MMPs, LM can enhance their expression and activity. They appear to be key matrix elements in the regulation of MMP activity via the recruitment of the CD44 receptor, a multiple MMP-interacting and activating platform playing an important role in cancer progression