Inflammatory Reactions in Microenvironments, Leading to Melanomagenesis

Abstract

Malignant melanoma is resistant to various therapies, while its incidence has been dramatically increasing. Among various factors, sun exposure, particularly ultra violet (UV) irradiation is considered to induce melanomas. Gangliosides have been markers of neuro-ectoderm-derived cancers like malignant melanomas and gliomas, but they also play crucial roles in their malignant properties. GD3 regulates cell signalling transduced through membrane microdomains. Chronic inflammatory reactions toward noxious stimuli cause cumbersome diseases such as cancers and degeneration, and glycosylation is involved in those processes. Here, melanocytes did not respond to UVB, while keratinocytes responded to UVB by secreting various cytokines such as TNFα and IL-6. Furthermore, these cytokines induced expression of melanoma-associated ganglioside GD3 on melanocytes. Expression of GD3 does not necessarily induce melanomas, but may form microenvironments for the generation of melanomas after long-term continuation. Consequently, combination of DNA mutagenesis and chronic inflammatory reaction seems to be critical for the melanomagenesis. Thus, 1. Mechanisms for the induction of GD3 synthase gene by inflammatory cytokines. 2. Meaning of GD3 expression in melanocytes. 3. Linkage between GD3 expression in melanocytes and melanomagenesis. 4. Prevention of UV exposure, are proposed as urgent issues to be solved in the near future.