title: Altered sphingolipid metabolism induced by tumor hypoxia - new vistas in glycolipid tumor markers.
abstract: 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.
authors.affiliation: Department of Molecular Pathology, Aichi Cancer Center, Nagoya 464-8681, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.forename: Keiko
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Shaner
authors.forename: Alfred H
authors.initials: AH
authors.lastname: Merrill
authors.forename: Reiji
authors.initials: R
authors.lastname: Kannagi
mesh_terms: 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*
chemical_list: D014408:Biomarkers, Tumor; D002518:Ceramides; D006017:Glycolipids; D013107:Sphingolipids