Enhanced expression of hydroxylated ceramide in well-differentiated endometrial adenocarcinoma.
Enhanced expression of hydroxylated ceramide in well-differentiated endometrial adenocarcinoma.
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高分化子宫内膜腺癌中羟基化神经酰胺的表达增强。
DOI：
10.3892/ol.2016.5410
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发表时间：
2017-01
期刊：
影响因子：
2.9
通讯作者：
Mikami M
中科院分区：
文献类型：
--
作者：
Tajima T;Miyazawa M;Hayashi M;Asai S;Ikeda M;Shida M;Hirasawa T;Iwamori M;Mikami M
根据我们以前对人子宫内膜中性糖脂的分析，本作者已经报告了葡萄糖基神经酰胺、乳糖基神经酰胺和球三糖神经酰胺(Gb3Cer)的浓度在月经周期的黄体期显著增加。众所周知，低分化子宫内膜腺癌比高分化子宫内膜腺癌进展更快，对治疗的反应更差。为探讨高分化和低分化子宫内膜癌的分子背景，测定了不同分化程度的子宫内膜癌组织中中性糖脂的水平。采用脂类提取、酶消化、薄层层析(TLC)、气-液色谱(GC)和质谱法等生化分析方法，测定肿瘤组织中中性糖脂的组成，并对高分化子宫内膜癌中特异表达的神经酰胺结构进行研究。高分化腺癌含有许多结构未知的糖脂，它们的迁移速度比Gb4Cer慢。在Gb3Cer中，在高分化癌的TLC上出现了三条带，而在低分化癌中只出现了两条带。这种差异与神经酰胺的脂肪酸组成有关，因为≥20碳原子的非羟基脂肪酸在高分化癌中增加，而α-羟基脂肪酸在低分化癌中增加。同样，在高分化癌中Gb4Cer的TLC上有两条带，而在低分化癌中只有一条带，在高分化癌中观察到神经酰胺的长链碱基含有植酸鞘糖苷。在子宫内膜癌中，神经酰胺分子的结构随肿瘤分化程度的不同而改变。这些发现提示羟化神经酰胺与子宫内膜腺癌的高分化表型有关。
Based on our previous analysis of neutral glycolipids in the human endometrium, the present authors already reported that the concentrations of glucosylceramide, lactosylceramide and globotriaosylceramide (Gb3Cer), in which both fatty acids and sphingosines in the ceramides are hydroxylated, exhibit a marked increase during the luteal phase of the menstrual cycle. It is also well known that poorly differentiated endometrial adenocarcinoma exhibits a more rapid progression and a worse response to therapy than well-differentiated endometrial adenocarcinoma. To examine the molecular background of well-differentiated and poorly differentiated cancers, the levels of neutral glycolipids in tumor tissues from endometrial carcinoma displaying different degrees of differentiation were measured. The composition of neutral glycolipids in tumor tissues was determined, and ceramide structures that were specifically expressed in well-differentiated endometrial carcinomas were investigated using biochemical analytical methods, including lipid extraction, enzyme digestion, thin-layer chromatography (TLC), gas-liquid chromatography and mass spectrometry. Well-differentiated adenocarcinoma contained numerous structurally unknown glycolipids that exhibited slower migration than globotetraosylceramide (Gb4Cer). In the case of Gb3Cer, three bands appeared on TLC in well-differentiated cancer, but only two bands appeared in the poorly-differentiated cancer. This difference was associated with the fatty acid composition of ceramide, since non-hydroxy fatty acids with ≥20 carbon atoms were increased in well-differentiated cancer, while α-hydroxy fatty acids were increased in poorly differentiated cancer. Similarly, there were two bands on TLC of Gb4Cer from well-differentiated cancer, but only one band in poorly differentiated cancer, and the long-chain base of ceramide was observed to contain phytosphingosine in well-differentiated cancer. It was demonstrated in endometrial cancer that the structure of ceramide molecules changes with the extent of tumor differentiation. These findings suggest that hydroxylated ceramides contribute to the well-differentiated phenotype of endometrial adenocarcinoma.
DOI：
10.1111/j.1349-7006.2002.tb01215.x
发表时间：
2002-10
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Takehara K;Kubushiro K;Kiguchi K;Ishiwata I;Tsukazaki K;Nozawa S;Iwamori M
通讯作者：
Iwamori M