Altered sphingolipid metabolism induced by tumor hypoxia - New vistas in glycolipid tumor markers

作者：Yin Jun; Miyazaki Keiko; Shaner Rebecca L; Merrill Alfred H Jr; Kannagi Reiji^*

来源：FEBS LETTERS, 2010, 584(9): 1872-1878.

DOI：10.1016/j.febslet.2009.11.019

• N-Glycolyl sialic acid
• Dihydroceramide synthesis
• Fatty acid 2-hydroxylase
• Dihydroceramide Delta4-desaturase-1/2
• Hypoxia-inducible factor
• Unsaturated very long-chain fatty acid

Uncontrolled growth of malignant cells produces hypoxic regions in locally advanced tumors. Recently we showed that tumor hypoxia-induced transcription of multiple genes involved in glycan synthesis, leading to expression of useful glycolipid tumor markers, such as gangliosides having N-glycolyl sialic acid. Our subsequent studies indicated that the ceramide portion of glycolipids, as well as their glycan moiety, was also significantly affected by hypoxia. Tumor hypoxia-induced marked accumulation of sphinganine (dihydrosphingosine) long-chain base, and significant reduction of unsaturated very long-chain fatty acids in the ceramide moiety. Mass-spectrometry, which yields information on both glycan- and ceramide moieties, is expected to be clinically useful in detecting such distinct molecular species of cancer-associated glycolipids having combined alteration in both glycan- and ceramide moieties.

• 出版日期2010-5-3