The epidermal integrin-mediated secretome regulates the skin microenvironment during tumorigenesis and repair

Integrins are cellular transmembrane receptors that physically connect the cytoskeleton with the extracellular matrix. As such, they are positioned to mediate cellular responses to microenvironmental cues. Importantly, integrins also regulate their own microenvironment through secreted factors, also known as the integrinmediated secretome. Epidermal integrins, or integrins expressed by keratinocytes of the skin epidermis, regulate the cutaneous microenvironment through the contribution of matrix components, via proteolytic matrix remodeling, or by mediating factors like cytokines and growth factors that can promote support for nearby but distinct cells of the stroma, such as immune cells, endothelial cells, and fibroblasts. This role for integrins is enhanced during both pathological and repair tissue remodeling processes, such as tumor growth and progression and wound healing. This review will discuss examples of how the epithelial integrin-mediated secretome can regulate the tissue microenvironment. Although different epithelial integrins in various contexts will be explored, emphasis will be given to epidermal integrins that regulate the secretome during wound healing and cutaneous tumor progression. Epidermal integrin alpha 3(31 is of particular focus as well, since this integrin has been revealed as a key regulator of the keratinocyte secretome.