Differences in Latency and Inducibility of Mouse Skin Melanomas Depending on the Age and Anatomic Site of the Skin¹

To determine whether the occurrence of skin melanoma is influenced by the age or the anatomic source of the skin in melanoma-susceptible transgenic mouse models, skin was grafted from donors of different ages or from different anatomic sites to a standard (lateral trunk) site in adult recipients of the same transgenic strain. In 27 grafts of neonatal body skin, melanomas arose with a significantly shorter latency than in 37 grafts of older body skin. The difference may reflect not only the larger number of extrafollicular melanocytes in a given area of neonatal skin but also their unusually high mitotic activity shortly after birth and the influence of other growing skin cells nearby. Each of these body-skin grafts usually developed a single tumor situated near the graft edge. Because maximal wound healing occurs at the edge of such full-thickness skin grafts, melanocytes near the edge would receive the highest exposure to growth factors and cytokines associated with wound healing. In contrast to these results, grafts of snout skin yielded many melanomas, each originating from melanocytes within a vibrissa follicle rather than at the graft edge. The relatively strong local tumorigenic stimulus may be attributable to intrafollicular growth factors normally involved in whisker growth. The above-described experiments support the conclusion that agents in the immediate skin environment of the melanocyte, in addition to the state of the melanocyte itself, contribute to melanoma formation.