Non-Ionizing Radiation Laboratory, STUK-Radiation and Nuclear Safety Authority, Laippatie 4, FIN-00880, Helsinki, Finland.
Cancer Cell Int. 2011 Jun 6;11(1):16. doi: 10.1186/1475-2867-11-16.
We have previously shown in vitro that UVA increases the adhesiveness of mouse B16-F1 melanoma cells to endothelium.We have also shown in vivo that UVA exposure of C57BL/6 mice, i.v. injected with B16-F1 cells, increases formation of pulmonary colonies of melanoma. The aim of the present animal study was to confirm the previously observed in vivo UVA effect and to determine whether in vitro UVA-exposure of melanoma cells, prior the i.v. injection, will have an enhancing effect on the pulmonary colonization capacity of melanoma cells. As a second aim, UVA-derived immunosuppression was determined.
Mice were i.v. injected with B16-F1 cells into the tail vein and then immediately exposed to UVA. Alternatively, to study the effect of UVA-induced adhesiveness on the colonization capacity of B16-F1 melanoma, cells were in vitro exposed prior to i.v. injection. Fourteen days after injection, lungs were collected and the number of pulmonary nodules was determined under dissecting microscope. The UVA-derived immunosuppression was measured by standard contact hypersensitivity assay.
Obtained results have confirmed that mice, i.v. injected with B16-F1 cells and thereafter exposed to UVA, developed 4-times more of melanoma colonies in lungs as compared with the UVA non-exposed group (p < 0.01). The in vitro exposure of melanoma cells prior to their injection into mice, led only to induction of 1.5-times more of pulmonary tumor nodules, being however a statistically non-significant change. The obtained results postulate that the UVA-induced changes in the adhesive properties of melanoma cells do not alone account for the 4-fold increase in the pulmonary tumor formation. Instead, it suggests that some systemic effect in a mouse might be responsible for the increased metastasis formation. Indeed, UVA was found to induce moderate systemic immunosuppression, which effect might contribute to the UVA-induced melanoma metastasis in mice lungs.
我们之前已经在体外证明，UVA 会增加小鼠 B16-F1 黑色素瘤细胞与内皮细胞的黏附性。我们还在体内证明，C57BL/6 小鼠经静脉注射 B16-F1 细胞后，暴露于 UVA 会增加黑色素瘤肺集落的形成。本动物研究的目的是确认之前观察到的体内 UVA 作用，并确定黑色素瘤细胞在静脉注射前体外暴露于 UVA 是否会增强黑色素瘤细胞的肺定植能力。第二个目的是确定 UVA 引起的免疫抑制作用。
将 B16-F1 细胞静脉注射到小鼠尾静脉中，然后立即暴露于 UVA。或者，为了研究 UVA 诱导的黏附性对 B16-F1 黑色素瘤定植能力的影响，在静脉注射前对细胞进行体外暴露。注射后 14 天，收集肺部并在解剖显微镜下确定肺结节的数量。通过标准接触超敏反应测定法测量 UVA 引起的免疫抑制作用。
结果证实，与未暴露于 UVA 的组相比，静脉注射 B16-F1 细胞后再暴露于 UVA 的小鼠肺部黑色素瘤集落增加了 4 倍（p < 0.01）。在将黑色素瘤细胞注射到小鼠之前进行体外暴露，仅导致肺肿瘤结节增加了 1.5 倍，但统计学上无显著变化。研究结果表明，黑色素瘤细胞黏附特性的 UVA 诱导变化本身并不能解释肺部肿瘤形成增加的 4 倍。相反，它表明在小鼠体内可能存在某种系统性影响，导致转移形成增加。事实上，发现 UVA 会引起中度系统性免疫抑制，这种作用可能有助于 UVA 诱导的黑色素瘤在小鼠肺部的转移。
