Solar exposure, the melanocyte and melanoma: Survival pathways and molecular mechanisms.
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Abstract
The keratinocyte and the melanocyte, the main cellular constituents of the epidermis, are two very different cell types. Despite their different origins and functionality, they come together in the skin, synergistically, to function as a unit to control the adverse effects of solar exposure. The most significant element in this protective process is the ability of the melanocyte to produce melanin. This pigmented polymer is responsible for constitutive skin colour that plays a part in our identity as human individuals but more importantly, provides a tanning response. A change in pigmentation that provides both an immediate and prolonged protective effect from the damaging components of solar radiation.
The melanocortin 1 receptor, a cell surface receptor on the melanocyte, receives paracrine stimulation in the form of hormonal communication from the keratinocyte, initiating a series of intracellular molecular interactions in the melanocyte, eventually involving transcription factors in the nucleus, most notably the microphthalmia-associated transcription factor, resulting in upregulation of enzymatic production of melanin and finally, its transfer back to the keratinocyte.
The melanocortin 1 receptor is highly polymorphic and unfortunately this results in the Caucasians’ having constitutionally fairer skin combined with an incomplete tanning response, resulting in a higher susceptibility to skin cancer.
The melanocyte is a relatively long-lived cell and over its extended life span can accumulate a series of mutational events. With malignant transition to melanoma this oncogenic baggage, when combined with antiapoptotic machinery that helps melanocyte survival, resulting in relatively rapid progression of the malignant process and contributing to its resistance to therapeutics.
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