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Altered sphingolipid metabolism induced by tumor hypoxia – New vistas in glycolipid tumor markers
Author(s) -
Yin Jun,
Miyazaki Keiko,
Shaner Rebecca L.,
Merrill Alfred H.,
Kannagi Reiji
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.11.019
Subject(s) - glycolipid , ceramide , sphingolipid , glycan , biochemistry , moiety , chemistry , sialic acid , glycosphingolipid , hypoxia (environmental) , biology , glycoprotein , oxygen , stereochemistry , apoptosis , organic chemistry
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.