Matrikines and matricryptins: Implications for cutaneous cancers and skin repair

Dermatologists are faced daily with the need to optimize skin repair and excise cutaneous cancers. The extracellular matrix plays a pivotal role in cellular migration, proliferation, and gene regulation during wound healing and progression of melanoma, basal cell carcinoma, and squamous cell carcinoma. Within the last few years, a new class of ligand, the matrikine or matricryptin, has been characterized as subdomains of various ECM proteins capable of signaling to the cell through receptors, such as growth factor receptors. Two classes exist: the "natural" matrikines, which signal directly from the extracellular milieu and "cryptic" matrikines (matricryptins) that require proteolytic processing to reveal the ligand or to release the ligand from its ECM protein. Unlike traditional soluble growth factors, most matrikines possess low binding affinity to their receptors and are often presented in multiple valency that likely increase avidity to receptors. The presentation of these ligands within the ECM can result in unique outcomes. The EGF-like repeats of tenascin-C and laminin-5 signal to EGFR preferentially to upregulate migration during skin repair and tumor progression. Other matrikines in collagen, elastin, decorin, and laminin-1 can promote chemotaxis, mitogenesis, and metastasis in cancers, such as melanoma. Finally, the unique properties of matrikines have been utilized in cancer therapeutics and tissue engineering. Within the next few years, the nature and function of this emerging class of matrikine ligands will have an impact on dermatology, as these proteins are altered in wound repair and skin diseases.