Systemic Circulating Leptin – Aiding New Dimension of Immune-Related Skin Carcinogenesis and Lipid Metabolism

Abstract

AIM: The link between the development of melanoma skin cancer and obesity is gaining recently an increased attention. A plethora of immune-related factors sustain a chronic inflammatory state modulated by the metabolic imbalance, the main examples being tumor necrosis factor alpha, interleukin 6, monocyte chemoattractant protein (MCP1), and several adipokines. Among the adipokines leptin (LEP) is steadily increasing interests as it involved in modulating different signaling pathways (e.g., JAK2/STAT3 and MAPK cascade/FOS) and immune cells fate by promoting the switch of memory cells to T helper-1 cell response, increases CD4+CD25- T-cell proliferation, and reduces autophagy during T-cell receptor stimulation. Our work investigates in a pilot study, using protein microarray technology, the LEP circulatory levels in melanoma patients in comparison to other cytokines and chemokines already reported as significantly involved in melanoma initiation and progression. METHODS: Serum from melanoma cases and pool of serum from healthy volunteers were analyzed by an antibody array platform for a 42-cytokine profile. RESULTS: The investigation of cytokines, chemokines, and growth factors has shown that all the proinflammatory circulating molecules are elevated in the melanoma patient’s serum. Inflammatory cytokines were found elevated and were correlated to the more advanced stage of the investigated patient (M2). The highest circulatory level was registered for LEP in both melanoma cases; moreover, in M1 patient, although the LEP level was completely comparable with the one found in M2, its IL-1 serum level was normal. In addition, there are ten analytes that show clear abnormal values and in patient M2 high LEP concentration is correlated with high IL-1, MCP-2, MCP-3, MCSF, and TARC serum concentrations. CONCLUSION: Leptin is pleiotropic adipocytokine involved in various diseases, including skin cancer and melanoma. As it is involved in favoring inflammation and further tumorigenesis, the development of effective leptin-based therapeutic approaches opens new possibilities of adjuvant therapy in skin cancers.