Extrafollicular dermal melanocyte stem cells and melanoma.

Extrafollicular dermal melanocyte stem cells and melanoma.
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DOI:
10.1155/2012/407079
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发表时间:
2012
影响因子:
4.3
通讯作者:
Weiswasser B
Weiswasser B
中科院分区:
医学3区
文献类型:
--
作者:
Hoerter JD;Bradley P;Casillas A;Chambers D;Denholm C;Johnson K;Weiswasser B

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最近的研究表明,毛囊外真皮黑素细胞干细胞(MSCs)出生后仍然存在于周围神经的浅层神经鞘中,当需要在皮肤的基底层替换表皮黑素细胞时,会产生迁移的黑素细胞前体细胞。如果能够证明受损的MSC或黑素细胞前体是黑色素瘤的主要来源,靶向识别并通过基于抗体的治疗来根除它将是治疗黑色素瘤的最佳方法,也是防止其复发的非常有效的方法。现对参与MSC自我更新、扩增和分化的转录因子和信号通路进行综述。提出了一个模型来说明长期UVA/UVB辐射对DNA的有害影响和MSCs的修复机制如何将它们转化为黑色素瘤干细胞。斑马鱼在研究间充质干细胞在黑色素瘤发生发展中的作用方面具有许多优势。斑马鱼体内调控MSCs发育的信号通路与在人类和老鼠身上发现的非常相似。能够很容易地操纵MSC数量,使斑马鱼成为研究对MSCs的损害可能导致黑色素瘤的极佳模型。
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.
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