title: Increased sialidase activity in serum of cancer patients: Identification of sialidase and inhibitor activities in human serum.
abstract: Aberrant sialylation in glycoproteins and glycolipids is a characteristic feature of malignancy. Human sialidases, which catalyze the removal of sialic acid residues from glycoconjugates, have been implicated in cancer progression. They have been detected in a wide variety of human cells and tissues, but few studies have focused on their existence in human serum. Among the four types identified to date, we previously demonstrated that plasma membrane-associated ganglioside sialidase (NEU3) is markedly upregulated in various human cancers, including examples in the colon and prostate. Here, using a sensitive assay method, we found a significant increase of sialidase activity in the serum of patients with prostate cancer compared with that in healthy subjects having low activity, if any. Activity was apparent with gangliosides as substrates, but only to a very limited extent with 4-methylumbelliferyl sialic acid, a good synthetic substrate for sialidases other than human NEU3. The serum sialidase was also almost entirely immunoprecipitated with anti-NEU3 antibody, but not with antibodies for other sialidases. Interestingly, sera additionally contained inhibitory activity against the sialidase and also against recombinant human NEU3. The sialidase and inhibitor activities could be separated by exosome isolation and by hydrophobic column chromatography. The serum sialidase was assessed by a sandwich ELISA method using two anti-NEU3 antibodies. The results provide strong evidence that the serum sialidase is, in fact, NEU3, and this subtype may, therefore, be a potential utility for novel diagnosis of human cancers.
authors: Division of Cancer Glycosylation Research, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, Japan.
authors: Keiko
authors: K
authors: Hata
authors: Tatsuo
authors: T
authors: Tochigi
authors: Ikuro
authors: I
authors: Sato
authors: Sadafumi
authors: S
authors: Kawamura
authors: Kazuhiro
authors: K
authors: Shiozaki
authors: Tadashi
authors: T
authors: Wada
authors: Kohta
authors: K
authors: Takahashi
authors: Setsuko
authors: S
authors: Moriya
authors: Kazunori
authors: K
authors: Yamaguchi
authors: Masahiro
authors: M
authors: Hosono
authors: Taeko
authors: T
authors: Miyagi
mesh_terms: D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D008297:Male; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood* / Q000276:immunology; D011471:Prostatic Neoplasms / Q000097:blood*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D005732:Gangliosides; D011994:Recombinant Proteins; C491428:NEU4 protein, human; C465436:Neu3 protein, human; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid
keywords: Cancer serum; diagnostic marker; ganglioside; prostate cancer; sialidase
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