文章：

从黑色素细胞到黑色素瘤的过程

The journey from melanocytes to melanoma

原文发布日期：2023-04-24

DOI: 10.1038/s41568-023-00565-7

类型: Review Article

开放获取: 否

英文摘要：

Over the past decade, melanoma has led the field in new cancer treatments, with impressive gains in on-treatment survival but more modest improvements in overall survival. Melanoma presents heterogeneity and transcriptional plasticity that recapitulates distinct melanocyte developmental states and phenotypes, allowing it to adapt to and eventually escape even the most advanced treatments. Despite remarkable advances in our understanding of melanoma biology and genetics, the melanoma cell of origin is still fiercely debated because both melanocyte stem cells and mature melanocytes can be transformed. Animal models and high-throughput single-cell sequencing approaches have opened new opportunities to address this question. Here, we discuss the melanocytic journey from the neural crest, where they emerge as melanoblasts, to the fully mature pigmented melanocytes resident in several tissues. We describe a new understanding of melanocyte biology and the different melanocyte subpopulations and microenvironments they inhabit, and how this provides unique insights into melanoma initiation and progression. We highlight recent findings on melanoma heterogeneity and transcriptional plasticity and their implications for exciting new research areas and treatment opportunities. The lessons from melanocyte biology reveal how cells that are present to protect us from the damaging effects of ultraviolet radiation reach back to their origins to become a potentially deadly cancer.

摘要翻译： 

过去十年，黑色素瘤引领了癌症治疗新方向，治疗生存期显著延长，但总生存期的改善较为有限。黑色素瘤呈现的异质性和转录可塑性重现了不同黑素细胞发育状态与表型，使其能够适应甚至最终逃逸最先进的治疗方案。尽管我们对黑色素瘤生物学和遗传学的认知取得显著进展，但其起源细胞仍存激烈争议，因为黑素干细胞和成熟黑素细胞均可能发生转化。动物模型和高通量单细胞测序技术为解决这一问题开辟了新途径。本文探讨黑素细胞从神经嵴（作为黑素母细胞起源）到定居多种组织成为完全成熟色素化黑素细胞的发育历程，阐述对黑素细胞生物学、不同黑素细胞亚群及其所处微环境的新认知，如何为揭示黑色素瘤发生发展机制提供独特视角。我们聚焦黑色素瘤异质性与转录可塑性的最新发现及其对新兴研究领域和治疗策略的启示。黑素细胞生物学的启示在于：这些原本保护我们免受紫外线伤害的细胞，如何通过追溯其发育起源而演变成致命癌症。

原文链接：

The journey from melanocytes to melanoma