Why do melanomas get so dark?
Why do melanomas get so dark?
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DOI：
10.1111/j.1600-0625.2009.00933.x
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发表时间：
2009-11-01
影响因子：
3.6
通讯作者：
Pawelek, John M.
中科院分区：
文献类型：
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作者：
Lazova, Rossitza;Pawelek, John M.
皮肤恶性黑色素瘤通常呈现出比周围皮肤颜色更深的色素沉着区域。虽然黑色素瘤细胞是黑色素的原始来源，但角质形成细胞和噬黑素细胞也对肿瘤颜色有影响，因为它们含有从黑色素瘤细胞获取的黑色素。然而，对于深色黑色素瘤细胞的起源以及调节其黑色素生成的分子途径知之甚少。在此我们讨论一些观察结果，即深色黑色素瘤细胞从原位黑色素瘤群体中产生，并且除了产生大量深色色素外，它们似乎还在发生自噬。此外，自噬似乎是真皮内侵袭性黑色素瘤细胞的一个共同特征。这种现象的根本原因可能源于被称为β1,6 - 分支寡糖的糖基化结构的异常产生。我们对深色皮肤黑色素瘤的研究是由对在实验室中融合的实验性小鼠巨噬细胞 - 黑色素瘤杂交细胞的分析所推动的。与皮肤恶性黑色素瘤中的黑色素瘤细胞一样，实验性杂交细胞也显示出大量深色色素和自噬，并且具有高水平的β1,6 - 分支寡糖。深色恶性黑色素瘤细胞是否源自体内与巨噬细胞的融合仍有待确定。无论如何，黑色素瘤中的色素沉着，长期以来被视为恶性肿瘤的次要方面，可能是细胞已获得侵袭和转移能力的一个可见警示。
Cutaneous malignant melanomas often exhibit pigmented regions that are darker than the surrounding skin. While melanoma cells are the original source of the melanin, keratinocytes and melanophages also contribute to the tumor colour because they contain melanin obtained from melanoma cells. However, little is known of the origin of darkly pigmented melanoma cells or of the molecular pathways regulating their melanin production. Here we discuss observations that dark melanoma cells emerge from within populations of melanoma in situ and that, in addition to producing abundant dark pigment, they appear to be undergoing autophagy. Moreover, autophagy appears to be a common trait of invasive melanoma cells in the dermis. The underlying cause of this phenomenon may stem from aberrant production of glycosylation structures known as beta 1,6-branched oligosaccharides. Our studies of dark cutaneous melanomas were prompted by analyses of experimental mouse macrophage-melanoma hybrids fused in the laboratory. Like melanoma cells in cutaneous malignant melanoma, experimental hybrids also displayed abundant dark pigment and autophagy, and had high levels of beta 1,6-branched oligosaccharides. Whether or not darkly pigmented malignant melanoma cells originate from fusion with macrophages in vivo remains to be determined. In any event, pigmentation in melanoma, long considered as a secondary aspect of the malignancy, may be a visible warning that the cells have gained competence for invasion and metastasis.