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New Perspectives on Melanoma_ The Role of PAX3

Melziman schoolofexercisebiomedicalandhealthsciences

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Unformatted text preview: ts located in the dermal component of the lesion, with melanoma samples showing larger number of PAX3, MCAM‐positive cells compared to naevi. This indicates that some PAX3‐positive cells in naevi and melanomas have the capability to undergo vertical spread/migration. It suggests that regulation of migration might be one of the roles of PAX3 in melanoma, as it is in development, where Pax3 regulates cMet [202]. The frequent observation of MCAM expression in cells of the hair follicle might be associated with downwards growth into the dermis and migration of follicular cells. The observation that some PAX3‐positive melanocytes in the ORS show MCAM expression, in contrast to those in the epidermis, suggests that MCAM is associated with migration of normal melanocytes from the bulge area to the developing hair follicle and to the epidermis. Upon reaching the epidermis, MCAM expression is downregulated. Alternatively, epidermal melanocytes do not arise and migrate from the bulge, but rather arise from interfollicular melanocyte stem 71 Chapter III – Medic and Ziman, 2010 cells, similar to those believed to maintain interfollicular epidermal homeostasis [165,267,268]. Even though some epidermal melanocytes resemble the transient amplifying melanocytic cells of the hair follicle with respect to their differentiation status, they are not thought to have the same migratory propensity. In summary, in addition to detection in the majority of naevus and melanoma cells, we conclusively show PAX3 expression in melanocytes of normal skin. Epidermal PAX3‐positive melanocytes, like follicular cells, exhibit a variable differentiation status; the majority show a more mature phenotype, but a proportion (around 20%) show a less differentiated and proliferative phenotype. Moreover, these melanocytes frequently show expression of a cell survival marker. Our results suggest that a previously identified role for PAX3, as a regulator of an undifferentiated plastic state, may operate in melanocytes of normal skin. This role, possibly required for cellular...
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