Department of Biological Sciences, Ferris State University, Big Rapids, MI 49307, USA.
Stem Cells Int. 2012;2012:407079. doi: 10.1155/2012/407079. Epub 2012 May 10.
Recent studies suggest that extrafollicular dermal melanocyte stem cells (MSCs) persist after birth in the superficial nerve sheath of peripheral nerves and give rise to migratory melanocyte precursors when replacements for epidermal melanocytes are needed on the basal epidermal layer of the skin. If a damaged MSC or melanocyte precursor can be shown to be the primary origin of melanoma, targeted identification and eradication of it by antibody-based therapies will be the best method to treat melanoma and a very effective way to prevent its recurrence. Transcription factors and signaling pathways involved in MSC self-renewal, expansion and differentiation are reviewed. A model is presented to show how the detrimental effects of long-term UVA/UVB radiation on DNA and repair mechanisms in MSCs convert them to melanoma stem cells. Zebrafish have many advantages for investigating the role of MSCs in the development of melanoma. The signaling pathways regulating the development of MSCs in zebrafish are very similar to those found in humans and mice. The ability to easily manipulate the MSC population makes zebrafish an excellent model for studying how damage to MSCs may lead to melanoma.
最近的研究表明，出生后真皮外毛细胞黑素干细胞（MSCs）存在于周围神经的浅层神经鞘中，当皮肤基底层的表皮黑素细胞需要替换时，它们会产生迁移性黑素细胞前体。如果受损的 MSC 或黑素细胞前体可以被证明是黑色素瘤的主要起源，那么通过基于抗体的治疗方法靶向识别和消除它将是治疗黑色素瘤的最佳方法，也是预防其复发的非常有效方法。本文综述了参与 MSC 自我更新、扩增和分化的转录因子和信号通路。提出了一个模型，以显示长期 UVA/UVB 辐射对 MSCs 中 DNA 和修复机制的有害影响如何将其转化为黑色素瘤干细胞。斑马鱼在研究 MSCs 在黑色素瘤发生中的作用方面具有许多优势。调节斑马鱼 MSCs 发育的信号通路与在人类和小鼠中发现的信号通路非常相似。由于能够轻松操纵 MSC 群体，斑马鱼成为研究 MSC 损伤如何导致黑色素瘤的理想模型。
