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 melanoma to the metastatic state is not very well defined. Although previous studies have concentrated on the effect of UV-B on the host immune response, the effect of UV-B on the tumor cells was not elucidated. Here we show that UV-B can induce interleukin 8 (IL-8) mRNA and protein secretion in human cutaneous melanoma with negligible expression of IL-8. UV-B-induced IL-8 was constitutively expressed 60 days after irradiation in tumors implanted in mice. Induction of IL-8 was UV-B dose dependent and blocked by cyclohexamide, indicating that de novo protein synthesis is required for its expression. The UV-irradiated cells demonstrated enhanced tumorigenicity and metastatic potential in nude mice. The increase in tumorigenicity and metastatic ability could be explained by the increase in Mr 72,000 type IV collagenase activity and angiogenesis attributed to the induction of IL-8 after irradiation. The acquisition of the metastatic phenotype induced by UV-B could not be attributed to abnormalities in the p53 or MTS-1 (p16INK4) genes. To the best of our knowledge, this is the first report to show that UV-B can increase the aggressiveness of human cutaneous melanoma for growth and metastasis.
Singh
R K
RK
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Gutman
M
M
Reich
R
R
Bar-Eli
M
M
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D017364:Collagenases / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D003513:Cycloheximide / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000096:biosynthesis*; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D020780:Matrix Metalloproteinase 9; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000235:genetics; D012878:Skin Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016209:Interleukin-8; D012333:RNA, Messenger; D003513:Cycloheximide; D017364:Collagenases; D020780:Matrix Metalloproteinase 9