Deglycosylation of serum vitamin D3-binding protein leads to immunosuppression in cancer patients.
Serum vitamin D3-binding protein (Gc protein) can be converted by beta-galactosidase of B cells and sialidase of T cells to a potent macrophage activating factor, a protein with N-acetylgalactosamine as the remaining sugar moiety. Thus, Gc protein is the precursor of the macrophage activating factor (MAF). Treatment of Gc protein with immobilized beta-galactosidase and sialidase generates an extremely high titered MAF, Gc-MAF. When peripheral blood monocytes/macrophages of 52 patients bearing various types of cancer were incubated with 100 pg/ml of GcMAF, the monocytes/macrophages of all patients were efficiently activated. However, the MAF precursor activity of patient plasma Gc protein was found to be severely reduced in about 25% of this patient population. About 45% of the patients had moderately reduced MAF precursor activities. Loss of the precursor activity was found to be due to deglycosylation of plasma Gc protein by alpha-N-acetylgalactosaminidase detected in the patient's bloodstream. The source of the enzyme appeared to be cancerous cells. Radiation therapy decreased plasma alpha-N-acetylgalactosaminidase activity with concomitant increase of precursor activity. This implies that radiation therapy decreases the number of cancerous cells capable of secreting alpha-N-acetylgalactosaminidase. Both alpha-N-acetylgalactosaminidase activity and MAF precursor activity of Gc protein in patient bloodstream can serve as diagnostic and prognostic indices.
Yamamoto
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Laboratory of Cancer Immunology and Molecular Biology, Albert Einstein Cancer Cener, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141, USA.
Naraparaju
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Asbell
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D000818:Animals; D005260:Female; D006031:Glycosylation; D006596:Hexosaminidases / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D008214:Lymphocytes / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology*; D009369:Neoplasms / Q000097:blood / Q000201:enzymology* / Q000276:immunology*; D011498:Protein Precursors / Q000528:radiation effects; D013379:Substrate Specificity; D014809:Vitamin D-Binding Protein / Q000097:blood* / Q000528:radiation effects; D001619:beta-N-Acetylhexosaminidases / Q000032:analysis
D011498:Protein Precursors; D014809:Vitamin D-Binding Protein; D006596:Hexosaminidases; D001619:beta-N-Acetylhexosaminidases