Chakraborty Ashok K, Pawelek John
Department of Dermatology and the Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520-8059, USA.
Melanoma Res. 2007 Feb;17(1):9-16. doi: 10.1097/CMR.0b013e3280114f34.
In previous studies, fusion of peritoneal macrophages or blood monocytes with mouse melanoma cells produced hybrids with upregulated expression of the glycosyltransferase beta1,6-N-acetylglucosaminyltransferase V (GnT-V) and its enzymatic product, beta1,6-branched oligosaccharides. This correlated with marked increases in motility, metastatic potential and, surprisingly, melanin content. This study was designed to establish direct roles for beta1,6-branched oligosaccharides in melanogenesis and motility. The levels of beta1,6-branched oligosaccharides were lowered by transfecting beta1,4-N-acetylglucosaminyltransferase III, a competitive inhibitor of GnT-V. beta1,4-N-acetylglucosaminyltransferase III transfection virtually eliminated melanin production and markedly decreased chemotactic motility. This implied that the metastatic and melanogenic phenotypes in hybrids were each upregulated by beta1,6-branched oligosaccharides. Although roles for beta1,6-branched oligosaccharides in motility and metastasis have been reported previously, this is the first study to directly implicate these structures in melanogenesis. Although drawn from experimental models, the findings might explain the well known hypermelanotic regions of human cutaneous malignant melanoma as hypermelanotic cutaneous malignant melanoma cells are rich in beta1,6-branched oligosaccharides. They might also explain why melanogenesis pathways differ between malignant and normal melanocytes as GnT-V is a myeloid-associated enzyme that is aberrantly expressed in melanoma cells but not in normal melanocytes.
在先前的研究中，腹膜巨噬细胞或血液单核细胞与小鼠黑色素瘤细胞融合产生了杂种细胞，其糖基转移酶β1,6-N-乙酰葡糖胺基转移酶V（GnT-V）及其酶产物β1,6-分支寡糖的表达上调。这与运动性、转移潜能的显著增加相关，令人惊讶的是，还与黑色素含量的增加相关。本研究旨在确定β1,6-分支寡糖在黑色素生成和运动性中的直接作用。通过转染β1,4-N-乙酰葡糖胺基转移酶III（GnT-V的竞争性抑制剂）降低β1,6-分支寡糖的水平。β1,4-N-乙酰葡糖胺基转移酶III转染几乎消除了黑色素的产生，并显著降低了趋化运动性。这表明杂种细胞中的转移和黑色素生成表型均由β1,6-分支寡糖上调。尽管先前已报道β1,6-分支寡糖在运动性和转移中的作用，但这是第一项直接表明这些结构参与黑色素生成的研究。尽管这些发现来自实验模型，但可能解释人类皮肤恶性黑色素瘤中众所周知的色素沉着过度区域，因为色素沉着过度的皮肤恶性黑色素瘤细胞富含β1,6-分支寡糖。它们还可能解释为什么恶性黑色素细胞和正常黑色素细胞之间的黑色素生成途径不同，因为GnT-V是一种与髓系相关的酶，在黑色素瘤细胞中异常表达，但在正常黑色素细胞中不表达。
