最新的《自然—细胞生物学》刊登一项研究称,科学家发现了一种因子,与先天性巨痣及其引起的黑色素瘤等出生胎记的形成和存在有着密切联系。该发现或能有助于开发针对恶性胎记的治疗新方法。
Olga Shakhova, Lukas Sommer等人对患有黑色素瘤的小鼠模型进行研究,该小鼠的黑色素瘤中含有已知的突变促进因子Nras,但缺少INK4a这种在人体黑色素瘤中并不活跃的因子。研究人员发现该小鼠模型和患有先天性巨痣以及黑色素瘤的人体具有显著的相似性。他们接着发现在小鼠和人身上获得的黑色素瘤和巨痣的样本中,一种名为Sox10的因子均含有较高的水平含量,先前研究已证明Sox10是神经嵴干细胞转化形成皮肤色素细胞的发育过程所必需的。研究人员进一步发现通过抑制神经嵴干细胞并阻断细胞的增殖和存活,可降低Sox10的水平含量,从而阻止黑色素瘤的形成。
由此研究人员得出结论:Sox10在先天性巨痣和黑色素瘤的形成和存在方面起着关键作用。这为开发出针对入侵性皮肤癌的治疗方法提供潜在的依据。(生物谷Bioon.com)
doi:10.1038/ncb2535
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Sox10 promotes the formation and maintenance of giant congenital naevi and melanomaOlga Shakhova,1 Daniel Zingg,1 Simon M. Schaefer,1 Lisette Hari,1 Gianluca Civenni,1 Jacqueline Blunschi,1 Stéphanie Claudinot,2 Michal Okoniewski,3 Friedrich Beermann,4 Daniela Mihic-Probst,5 Holger Moch,5 Michael Wegner,6 Reinhard Dummer,7 Yann Barrandon,2 Paolo Cinelli8, 9 & Lukas Sommer1Giant congenital naevi are pigmented childhood lesions that frequently lead to melanoma, the most aggressive skin cancer. The mechanisms underlying this malignancy are largely unknown, and there are no effective therapies. Here we describe a mouse model for giant congenital naevi and show that naevi and melanoma prominently express Sox10, a transcription factor crucial for the formation of melanocytes from the neural crest. Strikingly, Sox10 haploinsufficiency counteracts NrasQ61K-driven congenital naevus and melanoma formation without affecting the physiological functions of neural crest derivatives in the skin. Moreover, Sox10 is also crucial for the maintenance of neoplastic cells in vivo. In human patients, virtually all congenital naevi and melanomas are SOX10 positive. Furthermore, SOX10 silencing in human melanoma cells suppresses neural crest stem cell properties, counteracts proliferation and cell survival, and completely abolishes in vivo tumour formation. Thus, SOX10 represents a promising target for the treatment of congenital naevi and melanoma in human patients.