Extrafollicular Dermal Melanocyte Stem Cells and Melanoma

Recent studies suggest that extrafollicular dermal melanocyte stem cells (MSCs) persist after birth in the superficial nerve sheath of peripheral nerves and give rise to migratory melanocyte precursors when replacements for epidermal melanocytes are needed on the basal epidermal layer of the skin. If a damaged MSC or melanocyte precursor can be shown to be the primary origin of melanoma, targeted identification and eradication of it by antibody-based therapies will be the best method to treat melanoma and a very effective way to prevent its recurrence. Transcription factors and signaling pathways involved in MSC self-renewal, expansion and differentiation are reviewed. A model is presented to show how the detrimental effects of long-term UVA/UVB radiation on DNA and repair mechanisms in MSCs convert them to melanoma stem cells. Zebrafish have many advantages for investigating the role of MSCs in the development of melanoma. The signaling pathways regulating the development of MSCs in zebrafish are very similar to those found in humans and mice. The ability to easily manipulate the MSC population makes zebrafish an excellent model for studying how damage to MSCs may lead to melanoma

Effect of UVA Fluence Rate on Indicators of Oxidative Stress in Human Dermal Fibroblasts

During the course of a day human skin is exposed to solar UV radiation that fluctuates in fluence rate within the UVA (290-315 nm) and UVB (315-400 nm) spectrum. Variables affecting the fluence rate reaching skin cells include differences in UVA and UVB penetrating ability, presence or absence of sunscreens, atmospheric conditions, and season and geographical location where the exposure occurs. Our study determined the effect of UVA fluence rate in solar-simulated (SSR) and tanning-bed radiation (TBR) on four indicators of oxidative stress---protein oxidation, glutathione, heme oxygenase-1, and reactive oxygen species--in human dermal fibroblasts after receiving equivalent UVA and UVB doses. Our results show that the higher UVA fluence rate in TBR increases the level of all four indicators of oxidative stress. In sequential exposures when cells are exposed first to SSR, the lower UVA fluence rate in SSR induces a protective response that protects against oxidative stress following a second exposure to a higher UVA fluence rate. Our studies underscore the important role of UVA fluence rate in determining how human skin cells respond to a given dose of radiation containing both UVA and UVB radiation

Does Melanoma Begin in a Melanocyte Stem Cell?

What is the cellular origin of melanoma? What role do melanocyte stem cells (MSC) and other melanocyte precursors play in the development of melanoma? Are MSCs and other latent melanocyte precursors more susceptible to solar radiation? These and many other questions can be very effectively addressed using the zebrafish model. Zebrafish have a robust regenerative capability, permitting the study of how MSCs are regulated and recruited at specific times and places to generate the pigment pattern following fin amputation or melanocyte ablation. They can be used to determine the effects of environmental radiation on the proliferation, survival, repair, and differentiation of MSCs. Our lab is using zebrafish to investigate how UVA- (320–400 nm) and UVB- (290–320 nm) induced damage to MSCs may contribute to the development of melanoma. A review is given of MSCs in zebrafish as well as experimental techniques and drugs for manipulating MSC populations. These techniques can be used to design experiments to help answer many questions regarding the role of MSCs or melanocyte precursors in the formation of melanoma stem cells and tumors following exposure to UVA/UVB radiation

Effect of UVA Fluence Rate on Indicators of Oxidative Stress in Human Dermal Fibroblasts

<p>During the course of a day human skin is exposed to solar UV radiation that fluctuates in fluence rate within the UVA (290-315 nm) and UVB (315-400 nm) spectrum. Variables affecting the fluence rate reaching skin cells include differences in UVA and UVB penetrating ability, presence or absence of sunscreens, atmospheric conditions, and season and geographical location where the exposure occurs. Our study determined the effect of UVA fluence rate in solar-simulated (SSR) and tanning-bed radiation (TBR) on four indicators of oxidative stress---protein oxidation, glutathione, heme oxygenase-1, and reactive oxygen species--in human dermal fibroblasts after receiving equivalent UVA and UVB doses. Our results show that the higher UVA fluence rate in TBR increases the level of all four indicators of oxidative stress. In sequential exposures when cells are exposed first to SSR, the lower UVA fluence rate in SSR induces a protective response that protects against oxidative stress following a second exposure to a higher UVA fluence rate. Our studies underscore the important role of UVA fluence rate in determining how human skin cells respond to a given dose of radiation containing both UVA and UVB radiation.</p