2003 Fiscal Year Final Research Report Summary
Study on macrophage inactivation factors derived from head and neck cancers
| Project/Area Number |
13470445
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Matsumoto Dental University |
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Principal Investigator |
YAMAOKA Minoru Matsumoto Dental University, School of Dentistry, Professor, 歯学部, 教授 (50064671)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUURA Takashi Matsumoto Dental University, School of Dentistry, Assistant, 歯学部, 助手 (10298408)
TANAKA Hitoshi Matsumoto Dental University, School of Dentistry, Assistant Professor, 歯学部, 講師 (50267788)
UEMATSU Takashi Matsumoto Dental University, Graduate School of Oral Medicine, Associate Professor, 大学院・歯学独立研究科, 助教授 (40203476)
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| Project Period (FY) |
2001 – 2003
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| Keywords | macrophage activating factor (GcMAF) / a-N-acetylgalactosaminidase / head and neck cancer / cellular immunodeficiency / salivary gland adenocarcinoma |
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| Research Abstract |
The present study aimed to clarify whether human salivary gland adenocarcinoma cell-derived a-N-acetylgalactosaminidase (a-NaGalase) affects the bioactivity of an Ο-linked immune-related biomacromolecule, macrophage-activating factor (GcMAF). Compared to the squamous cell carcinoma cell line, SCCTM, high levels of exo-a-NaGalase activity were detected in cell extract and conditioning medium of the human salivary gland cell adenocarcinoma cell line HSG. Normal keratinocytes and fibroblasts exhibited low levels of exo-a-NaGalase activity. A protein from HSG was purified by ion exchange and gel filtration chromatography using exo-a-NaGalase activity assay as an indicator of fractionation. A characteristic study of the purified enzyme indicated that the enzyme hydrolyzes synthetic substrates and displays low intrinsic endo-a-NaGalase and a-galactosidase activities in addition to exo-a-NaGalase activity. Monocytes/macrophages incubated with HSG-derived a-NaGalase-treated GcMAF in the superoxide generation assay exhibited decreased superoxide-generation capacity compared to cells incubated with GcMAF alone. Phagocytic activity of monocytes/macrophages was increased by incubation with GcMAF, but not by HSG-derived a-NaGalase-treated GcMAF. In vitro deglycosylation of Gc protein using peanut agglutinin lectin, which recognizes galactose/N-acetylgalactosamine residues, demonstrated that HSG-derived a-NaGalase displays both exo-and endo-enzyme activities and facilitates sialidase activity. These results demonstrate that HSG-derived a-NaGalase possesses unique enzymatic properties compared to the constitutive enzyme of normal cells, and represents a candidate cellular immunodeficiency factor in the GcMAF related-immune cascade for host defense in cancer patients with salivary gland adenocarcinomas.
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