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

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.