| Project/Area Number |
12557214
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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 | 展開研究 |
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| Research Field |
Biological pharmacy
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| Research Institution | KOBE PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
SUGAHARA Kazuyuki KOBE PHARMACEUTICAL UNIVERSITY, Dept.of Biochemistry, Professor, 薬学部, 教授 (60154449)
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| Co-Investigator(Kenkyū-buntansha) |
MIKAMI Tadahisa KOBE PHARMACEUTICAL UNIVERSITY, Dept.of Biochemistry, Instructor, 薬学部, 助手 (20330425)
YAMADA Shuhei KOBE PHARMACEUTICAL UNIVERSITY, Dept.of Biochemistry, Lecturer, 薬学部, 講師 (70240017)
KITAGAWA Hiroshi KOBE PHARMACEUTICAL UNIVERSITY, Dept.of Biochemistry, Assistant Professor, 薬学部, 助教授 (40221915)
NAKAJIMA Motowo Novartis Pharma, K.K., Tsukuba Research Institute, Chief Scientist, 筑波研究所・研究本部, 主席研究員
NOMIZU Motoyoshi Hokkaido University, Graduate School of Environmental Earth Science, Assistant Professor, 大学院・地球環境科学研究科, 助教授 (00311522)
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| Project Period (FY) |
2000 – 2003
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| Keywords | heparan sulfate / heparin-binding growth factors / heparanase / tumor metastasis / chondroitin sulfate / EXT tumor suppressor genes / glycosyltransferases / amyloid precursor protein |
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| Research Abstract |
The major results can be classified into the following three categories.
1)The detailed substrate specificity was revealed for human heparanase that is involved in the tumor invasion and metastasis, which has provided the basic knowledge for developing the early diagnosis of cancers.
2)In addition to the EXT1/EXT2 complex; the requirement of the aglycon moiety for the acceptor substrate for the above enzyme complex, which catalyzes the polymerization of a heparan backbone, was demonstrated, and the polymerization was achieved for the first time. Furthermore, the recombinant human EXTL2 protein, which is likely involved in the regulation of heparan sulfate synthesis, was crystallized, and the crystallographic data have provided a clue to investigate the molecular mechanism of heparan sulfate synthesis.
3)It was demonstrated that the so-called heparin-binding growth factors, which utilize heparan sulfate as a co-receptor, can interact specifically also with chondroitin sulfate chains containing the "E" disaccharide units. The results suggested that chondroitin sulfate can also be applicable to the development of anti-cancer drugs. In addition, the chondroitin sulfate chain of an amyloid precuresorprotein appican produced by rat C6 glyoma cells, unlike the chondroitin sulfate chain of appican expressed in neuronal cells, was shown to contain the "E" units and specifically interact with heparin-binding growth factors. These findings suggested that the chondroitin sulfate chain produced by glial cells may regulate the functions of neuronal cells.
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