Neonatal susceptibility to UV induced cutaneous malignant melanoma in a mouse model

Abstract

UV irradiation has multiple effects on skin including erythema, immunosuppression and the induction of keratinocyte-derived skin cancers and cutaneous malignant melanoma (CMM). CMM which arises from damage to the melanocyte, the pigment cell of the skin, is associated in epidemiologic studies with sun-exposure of susceptible populations, especially children. Our experimental studies have supported the concept that the epidemiologically observed susceptibility in children has a biologic basis. Hepatocyte growth factor/scatter factor (HGF/SF) transgenic mice neonatally irradiated with UV produce melanomas which recapitulate human disease in histopathology and molecular pathogenesis. In this model, neonatal UV is necessary and sufficient for melanoma induction although an additional adult dose of UV radiation significantly increased melanoma multiplicity. One hypothesis for the susceptibility of neonatal mice to induction of melanoma is that neonatal skin contains a large number of immature melanocytes which may result in the retention of the consequences of UV damage throughout the lifetime of the animal. An alternate hypothesis is that the immaturity of the neonatal immune system results in tolerance to melanocytic antigens produced by UV exposure, thus permitting the subsequent outgrowth of melanoma. Here, we discuss the current state of knowledge about the differences between adult and neonatal mice in melanocytes and immune maturation as possible factors playing a role in the susceptibility to melanoma in UV irradiated HGF/SF transgenic mice.