Melanocyte and Melanoma Cell Activation by Calprotectin

Abstract

Calprotectin, a heterodimer of S100A8 and S100A9, is a proinflammatory cytokine released from ultraviolet radiation-exposed keratinocytes. Calprotectin binds to Toll-like receptor 4, the receptor for advanced glycation end-products, and extracellular matrix metalloproteinase inducer on target cells to stimulate migration. Melanocytes and melanoma cells produce little if any calprotectin, but they do express receptors for the cytokine. Thus, keratinocyte-derived calprotectin has the potential to activate melanocytes and melanoma cells within the epidermis in a paracrine manner. We examined the ability of calprotectin to stimulate proliferation and migration in normal human melanocytes and melanoma cells in vitro. We first showed, by immunofluorescence and quantitative RT-PCR, that the melanocytic cells employed expressed a calprotectin receptor, the receptor for advanced end-products. We then demonstrated that calprotectin significantly enhanced proliferation, migration, and Matrigel invasion in both normal human melanocytes and melanoma cells. Thus, calprotectin is one of the numerous paracrine factors released by ultraviolet radiation-exposed keratinocytes that may promote melanomagenesis and is a potential target for melanoma prevention or therapy.

Effects of unsaturated fatty acids (Arachidonic/Oleic Acids) on stability and structural properties of Calprotectin using molecular docking and molecular dynamics simulation approach

“…Due to absence of signal peptide sequence in the aforementioned complex, the protein secretion is done via an energy dependent PKC-activation procedure, not by endoplasmic reticulum-Golgi pathway [4,11,12]. Moreover, other cell lines including keratinocytes, chondrocytes and endothelial cells have the ability of Calprotectin expression and secretion under certain conditions [5,13]. The human S100A8/A9 can be considered as an antimicrobial agent due to the capability of the complex to bind to multiple metal ions.…”

TLR4 in skin cancer: From molecular mechanisms to clinical interventions

“…Moreover, paracrine factors secreted by keratinocytes in response to stress such as solar UV, HMGB1, and calprotectin (S100A8/A9 heterodimer) cause melanocyte and melanoma cell activation through TLR4 agonism . TLR4 signaling has also been shown to promote the migration of human melanoma cells .…”

Biomarkers in Malignant Melanoma: Recent Trends and Critical Perspective

“…S100A8/A9 stimulates cell proliferation and migration via the pattern recognition receptor RAGE (receptor for advanced glycation end products) (68). Because of the RAGE expression in melanocytes and melanoma cells, calprotectin seems to be an activator in these cells and it is a potential target for intervention in melanomagenesis (69). The latter should also be considered regarding interaction of S100A4 with RAGE (61,62).…”