Proteolytic processing of laminin and the role of cryptides in tumoral biology

During tumor progression and metastasis, neoplastic cells separate from a primary tumor and migrate through connective tissues and blood vessels. These events involve interactions of tumor cells with the basement membrane, a thin and flexible layer of highly specialized extracellular matrix. Basement membrane proteolysis is related to the invasive capacity of malignant tumors and promotes the rupture of the mechanical barrier represented by this structure, favoring tumor cell spread. Matrix metalloproteinases play a key role in basement membrane cleavage and can further enable exposure and release of protein domains capable of stimulating biological activities distinct from the intact molecule. These domains, known as cryptides, can be found in most extracellular matrix components. Laminin, a heterotrimeric basement membrane glycoprotein associated with cell adhesion, migration, differentiation, and proliferation, presents different cryptides with relevant biological activities. Among them, laminin-111 peptides YIGSR, IKVAV, AG73, and C16 are known for their ability to influence tumor behavior.