Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF-related macrophage activation

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• 作者：Mohamad ; Saharuddin B. ; Nagasawa ; Hideko ; Uto ; Yoshihiro ; Hori ; Hitoshi
• 关键词：Alpha-N-acetylgalactosaminidase ; Gal-beta-GalNAc-alpha-PNP ; GalNAc-alpha-PNP ; GcMAF-mediated macrophage activation cascade ; Gc protein-derived macrophage activating factor (GcMAF) ; Mouse peritoneal macrophage ; Superoxide ; Tumor cells
• 刊名：Comparative Biochemistry and Physiology - Part A: Molecular & Integrative Physiology
• 出版年：2002
• 出版时间：May, 2002
• 年：2002
• 卷：132
• 期：1
• 页码：1-8
• 全文大小：226 K

文摘

Alpha-N-acetyl galactosaminidase (alpha-NaGalase) has been reported to accumulate in serum of cancer patients and be responsible for deglycosylation of Gc protein, which is a precursor of GcMAF-mediated macrophage activation cascade, finally leading to immunosuppression in advanced cancer patients. We studied the biochemical characterization of alpha-NaGalase from several human tumor cell lines. We also examined its effect on the potency of GcMAF to activate mouse peritoneal macrophage to produce superoxide in GcMAF-mediated macrophage activation cascade. The specific activity of alpha-NaGalases from human colon tumor cell line HCT116, human hepatoma cell line HepG2, and normal human liver cells (Chang liver cell line) were evaluated using two types of substrates; GalNAc-alpha-PNP (exo-type substrate) and Gal-beta-GalNAc-alpha-PNP (endo-type substrate). Tumor-derived alpha-NaGalase having higher activity than normal alpha-NaGalase, had higher substrate specificity to the exo-type substrate than to the endo-type substrate, and still maintained its activity at pH 7. GcMAF enhance superoxide production in mouse macrophage, and pre-treatment of GcMAF with tumor cell lysate reduce the activity. We conclude that tumor-derived alpha-NaGalase is different in biochemical characterization compared to normal alpha-NaGalase from normal Chang liver cells. In addition, tumor cell-derived alpha-NaGalase decreases the potency of GcMAF on macrophage activation.