Melanocyte Pygmentation – Friend or Foe on the Route to Melanoma

Abstract

The epidermis forms the top protective covering of normal human skin and is itself composed of multiple layers from the stratum corneum at the top, to proliferating cells in the deep/basal layer (Liu & Fisher, 2010). The epidermal cell population is mainly constituted of two cell types: keratinocytes and melanocytes. Keratinocytes constitute the majority of the epidermis; they have a “supporting” and regulatory role for the melanocytes. Keratinocytes are linked through tight desmosomal intercellular junctions and also anchored into the basal membrane through hemidesmosomes, but melanocytes remain as singly scattered, unattached cells. Each single, well-differentiated, melanocyte interacts with 36 viable keratinocytes at various stages of progression to the upper cornified layer of the epidermis (Fitzpatrick & Breathnach, 1963) to form epidermal units. These structural and functional cellular units exhibit complex, life-long, cellular interactions originally laid down during embryonic life. There are considerable interindividual and intraindividual variations in melanocyte population densities, with more than twice as many melanocytes located in head and forearm skin compared with elsewhere on the body, as well as darker skin in the folded areas of axillae and perineum, traits that remain remarkably consistent between races (Szabo, 1967). Despite significant variation in skin pigmentation, the density of melanocytes at the epidermal-dermal junction is very similar across different skin types (Yamaguchi & Hearing, 2009). Thus the main contributor to racial differences in skin pigmentation is cellular activity rather than absolute melanocyte numbers (Szabo, 1967). Melanocytes play a central role in the response of skin to sunlight exposure. They are directly involved in UV-induced pigmentation as a defense mechanism. People with different skin color possess varied sensitivity to ultraviolet (UV) exposure, with darker skinned individuals being less susceptible to sun-induced skin alterations, including cancer, than fair skinned ones (Elwood & Diffey 1993). Such a difference can be explained in terms of protective UV filtering by epidermal pigmentation, because the skin color is also related to the type of melanin, the number, size, type, distribution and degradation of melanosomes, and the tyrosinase activity of melanocytes (Nordlund & Ortonne 1998, Yamaguchi & Hearing 2009). The decreased photocarcinogenesis seen in individuals with darker skin may also be attributed to the more efficient removal of UV-damaged cells (Yamaguchi & Hearing 2009, Alonso & Fuchs, 2003, Fuchs, 2008).