紫外线辐射诱导的炎症在黑色素瘤中促进血管化和转移
Tobias Bald1, Thomas Quast2, Jennifer Landsberg1
1Laboratory of Experimental Dermatology, Department of Dermatology and Allergy, University of Bonn, 53115 Bonn, Germany.
Nature
|February 28, 2014
概括
重复的紫外线 (UV) 暴露会通过引发炎症促进黑色素瘤转移. 这种紫外线诱导的炎症增强了黑色素瘤细胞沿着血管的入侵,并增加了肺转移,独立于DNA损伤.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 皮肤病学 皮肤病学
背景情况:
- 间歇性强紫外线 (UV) 辐射是黑色素瘤的已知原因,主要是通过DNA突变.
- 紫外线辐射对黑色素瘤病原体的微环境影响的影响仍然不完全理解.
研究的目的:
- 为了研究重复的紫外线暴露如何影响黑色素瘤转移,而不涉及其瘤发起的DNA损伤.
- 阐明紫外线辐射促进黑色素瘤进展的微环境机制.
主要方法:
- 利用一种基因工程小鼠原发性皮肤黑色素瘤模型.
- 用重复的紫外线照射来评估转移性进展和相关的细胞和分子变化.
- 研究了中性粒细胞,高流动性组盒1 (HMGB1) 和托尔类受体4 (TLR4) 在紫外线诱导的黑色素瘤转移中的作用.
主要成果:
- 重复的紫外线暴露增强了黑色素瘤细胞沿血管扩张,增加了肺转移.
- 这种转移性增强依赖于UV诱导的中性粒细胞招募和激活,由HMGB1和TLR4介导.
- 紫外线照射刺激了血管生成,并促进了黑色素瘤细胞向内皮细胞的迁移,从而导致周围血管入侵 (血管变).
结论:
- 紫外线诱导的炎症,通过状细胞衍生的HMGB1和通过TLR4激活中性粒细胞,驱动黑色素瘤转移.
- 血管向量,一个围血管入侵的机制,是由紫外线辐射促进,并有助于黑色素瘤的传播.
- 针对炎症诱导的黑色素瘤细胞可塑性和内皮细胞相互作用,提供了一个合理的策略来抑制转移.
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