UV-Induced Molecular Signaling Differences in Melanoma and Non-melanoma Skin Cancer

Abstract

There are three major types of skin cancer: melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC and SCC are often referred to as non-melanoma skin cancer (NMSC). NMSCs are relatively non-lethal and curable by surgery, hence are not reportable in most cancer registries all over the world. Melanoma is the deadliest skin cancer. Its incidence rate (case number) is about 1/10th of that for NMSC, yet its death toll is ~8 fold higher than NMSC.Melanomas arise from melanocytes which are normally located on the basement membrane with dendrites extending into the epidermal keratinocytes. A major known function of melanocytes is to produce pigments which are enclosed by lipid membrane (termed melanosomes) and distribute them into keratinocytes, thus give different shade of skin colors. BCCs arise from basal cells, which are a layer of cells located at the deepest part of epidermis. Basal cells are recently considered to be skin stem cells as they are constantly proliferating and generating keratinocytes which are continuously pushed to the surface and eventually become a dead layer of stratum corneum. Squamous cells are the keratinocytes which resembles fish scale shape, ie, those initiated from basal cells and differentiated into squamous cells. Both basal cells and squamous cells belong to keratinocytes, therefore sometimes BCC and SCC are termed keratinocyte cancer.These three types of cancer share many characteristics, yet they are very different from etiology to progression. One shared characteristic of skin cancer is that, according to the current views, they all are caused by solar or artificial ultraviolet radiation (UVR). UVA and UVB from solar UVR are the major UV bands reaching the earth surface. Both UV types cause DNA damage and immune suppression which play crucial roles in skin carcinogenesis. UVB can be directly absorbed by DNA molecules and thus causes UV-signature DNA damages; UVA, on the other hand, may function through inducing cellular ROS which then causes oxidative DNA damages [1-4]. This chapter will discuss the molecular signaling differences of UVR in melanoma and NMSC.

Copper/Zinc Superoxide Dismutase in Human Skin: Current Knowledge

“…Melanoma is rarer, but better known and more dangerous. Malignant skin tumors develop relatively slowly and are largely treatable if detected early and then treated promptly (80). Immunohistochemical analysis of BCC and SCC revealed a reduction of immunoreactive Cu/Zn SOD and Mn SOD, indicating a UV-dependent depletion of antioxidant defenses; this reduction seems to be inversely proportional to the proliferation of malignant cells (81).…”

Cannabinoids in the Pathophysiology of Skin Inflammation

“…The deadliest skin cancer with an increasing incidence, melanoma arises from melanocytes mainly subjected to solar or artificial ultraviolet radiation that induces DNA deterioration and enhances immune suppression [167,168].…”

Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies

“…Overexposure to sunlight is directly connected the with onset of skin cancers such as basal cell carcinoma (BSC) [ 165 ], squamous cell carcinoma (SCC) [ 166 , 167 ], and malignant melanoma (MM) [ 168 , 169 ]. The accumulation of unrepaired photolesions in the DNA and formation of ROS may cause mutations in proto-oncogenes or tumor suppressors (for example TP53 ) and lead to malignant transformation of cells.…”