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.
Yin
Jun
J
Department of Molecular Pathology, Aichi Cancer Center, Nagoya 464-8681, Japan.
Miyazaki
Keiko
K
Shaner
Rebecca L
RL
Merrill
Alfred H
AH
Kannagi
Reiji
R
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D002518:Ceramides / Q000032:analysis / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006017:Glycolipids / Q000032:analysis / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D052439:Lipid Metabolism Disorders / Q000209:etiology*; D013058:Mass Spectrometry / Q000379:methods; D008954:Models, Biological; D009369:Neoplasms / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D013107:Sphingolipids / Q000032:analysis / Q000378:metabolism*
D014408:Biomarkers, Tumor; D002518:Ceramides; D006017:Glycolipids; D013107:Sphingolipids