Autophagy in cutaneous malignant melanoma
Autophagy in cutaneous malignant melanoma
复制标题
DOI：
10.1111/j.1600-0560.2009.01359.x
复制
发表时间：
2010-02-01
影响因子：
1.7
通讯作者：
Pawelek, John
中科院分区：
文献类型：
--
作者：
Lazova, Rossitza;Klump, Vincent;Pawelek, John
我们发现恶性黑色素瘤细胞呈现出高水平的自噬现象。自噬是一种细胞质内蛋白质和细胞器的消化过程，在营养缺乏时可提供能量来源。在一组12例浅表扩散型皮肤恶性黑色素瘤病例中，原位增殖性黑色素瘤（MIS）细胞以及真皮内的浸润细胞似乎都在发生自噬。通过使用标记物LC3B（微管相关轻链3B）进行免疫组织化学检测以及电子显微镜观察，都发现了自噬体。一些自噬体包含黑色素化的黑素体，这解释了恶性黑色素瘤中“粗大黑色素”的现象。自噬体还包含高尔基体58k蛋白（高尔基体的一种结构成分）以及β1,6 - 分支寡糖，这表明至少一些自噬体蛋白质被这些结构糖基化。这些研究结果表明，自噬可能是浸润性和转移性黑色素瘤细胞的一种固有代谢状态。有趣的是，肿瘤相关的噬黑素细胞也表现出类似的表型。这些发现与先前关于内质网（ER）应激驱动黑色素瘤进展的报道一致，因为已知内质网应激会引发自噬。研究结果提示，抑制自噬的疗法可能通过剥夺细胞的一个重要能量来源而对恶性黑色素瘤的治疗有效。
We show that malignant melanoma cells display high levels of autophagy, a cytoplasmic process of protein and organelle digestion that provides an energy source in times of nutrient deprivation. In a panel of 12 cases of cutaneous malignant melanoma of the superficial spreading type, cells in florid melanoma in situ (MIS) and invasive cells in the dermis appeared to be undergoing autophagy. Autophagosomes were detected through immunohistochemistry using the marker LC3B (microtubule-associated light chain 3B), and by electron microscopy. Some autophagosomes contained melanized melanosomes, accounting for the phenomenon of 'coarse melanin' in malignant melanoma. Autophagosomes also contained the Golgi 58k protein, a structural component of the Golgi apparatus, and beta 1,6-branched oligosaccharides, indicating that at least some of the autophagosomal proteins were glycosylated with these structures. The findings suggest that autophagy could be a constitutive metabolic state for invasive and metastatic melanoma cells. Interestingly, a similar phenotype was also expressed by tumor-associated melanophages. The findings are consistent with previous reports that endoplasmic reticulum (ER) stress drives melanoma progression, since ER stress is known to trigger autophagy. The results suggest that therapies inhibiting autophagy may be effective for the treatment of malignant melanoma by depriving cells of an important energy source.