Singh R K, Gutman M, Reich R, Bar-Eli M
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Cancer Res. 1995 Aug 15;55(16):3669-74.
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.
紫外线辐射已被证明在人类皮肤黑色素瘤的起始过程中发挥作用,但其在恶性黑色素瘤发展至转移状态过程中的作用尚未明确界定。尽管先前的研究集中于紫外线B对宿主免疫反应的影响,但紫外线B对肿瘤细胞的影响尚未阐明。在此我们表明,紫外线B可在白细胞介素8(IL-8)表达可忽略不计的人类皮肤黑色素瘤中诱导IL-8信使核糖核酸及蛋白质分泌。紫外线B诱导的IL-8在植入小鼠的肿瘤中照射60天后持续表达。IL-8的诱导呈紫外线B剂量依赖性,并被环己酰亚胺阻断,表明其表达需要从头合成蛋白质。紫外线照射的细胞在裸鼠中表现出增强的致瘤性和转移潜能。致瘤性和转移能力的增加可通过照射后IL-8诱导导致的72,000分子量IV型胶原酶活性增加和血管生成来解释。紫外线B诱导的转移表型的获得不能归因于p53或MTS-1(p-16INK4)基因异常。据我们所知,这是首份表明紫外线B可增加人类皮肤黑色素瘤生长和转移侵袭性的报告。