de Gruijl Frank R, Tensen Cornelis P
Department of Dermatology, Leiden University Medical Center Leiden, Netherlands.
Front Med (Lausanne). 2018 May 29;5:165. doi: 10.3389/fmed.2018.00165. eCollection 2018.
UV radiation in sunlight has long been recognized as the main exogenous cause of skin carcinomas. We present a brief historical perspective on the progress in understanding the pathogenesis of skin carcinomas, and recent advances. Sun-exposed skin carries numerous UV-related mutations, and skin carcinomas rank among the tumors with the highest mutational loads. In this multitude of mutations only a few are crucial in driving the tumor. Some are known from hereditary (skin) cancer syndromes and other recurrent ones have been validated in transgenic mice. Considering the continuous renewal of the epidermis, the question arises whether the lifelong residing stem cells are the main targets in skin carcinogenesis, a multistep process that would require ample time to evolve. Therefore, classic quiescent stem cells have been studied as potential tumor-initiating cells, as well as more recently discovered actively dividing stem cells (either Lgr5+ or Lgr6+). Interesting differences have emerged between experimental UV and two-stage chemical carcinogenesis, e.g., the latter appears to originate from follicular stem cells, in contrast to the former.
长期以来，阳光中的紫外线一直被认为是皮肤癌的主要外源性病因。我们简要回顾一下在理解皮肤癌发病机制方面的进展及近期研究成果。暴露于阳光下的皮肤携带大量与紫外线相关的突变，皮肤癌是突变负荷最高的肿瘤之一。在众多突变中，只有少数对肿瘤的发生发展起关键作用。其中一些突变在遗传性（皮肤）癌综合征中已为人所知，其他一些反复出现的突变已在转基因小鼠中得到验证。考虑到表皮的持续更新，终身存在的干细胞是否是皮肤癌发生（这一需要足够时间演变的多步骤过程）的主要靶点这一问题随之而来。因此，经典的静止干细胞以及最近发现的活跃分裂干细胞（Lgr5 + 或Lgr6 +）都被作为潜在的肿瘤起始细胞进行了研究。实验性紫外线致癌与两阶段化学致癌之间出现了有趣的差异，例如，与前者相比，后者似乎起源于毛囊干细胞。
