ULTRAVIOLET-B IRRADIATION PROMOTES TUMORIGENIC AND METASTATIC PROPERTIES IN PRIMARY CUTANEOUS MELANOMA VIA INDUCTION OF INTERLEUKIN-8

UV radiation has been shown to play a role in the initiation of human cutaneous melanoma, but its role in the development of malignant melan oma to the metastatic state is not very well defined. Although previou s studies have concentrated on the effect of UV-B on the host immune r esponse, the effect of UV-B on the tumor tells was not elucidated. Her e we show that UV-B can induce interleukin 8 (IL-8) mRNA and protein s ecretion in human cutaneous melanoma with negligible expression of IL- 8. UV-B-induced IL-8 was constitutively expressed 60 days after irradi ation in tumors implanted in mice. Induction of IL-8 was UV-B dose dep endent and blocked by cyclohexamide, indicating that de novo protein s ynthesis is required for its expression. The UV-irradiated cells demon strated enhanced tumorigenicity and metastatic potential in nude mice. The increase in tumorigenicity and metastatic ability could be explai ned by the increase in M(r) 72,000 type IV collagenase activity and an giogenesis attributed to the induction of IL-8 after irradiation. The acquisition of the metastatic phenotype induced by UV-B could not be a ttributed to abnormalities in the p53 or MTS-1 (p16(INK4)) genes. To t he best of our knowledge, this is the first report to show that UV-B c an increase the aggressiveness of human cutaneous melanoma for growth and metastasis.