| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Miki Tokyo Medical and Dental University, Graduate School, Lecturer, 大学院・医歯学総合研究科, 講師 (70191533)
KATARZYNA anna podyma Tokyo Medical and Dental University, Faculty of Dentistry, Teaching Stuff, 歯学部, 教務職員 (90302877)
SHINOMURA Tamayuki Tokyo Medical and Dental University, Graduate School, Assosiate Professor, 大学院・医歯学総合研究科, 助教授 (70206118)
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| Research Abstract |
The extracellular matrix is one of the major constituents of connective tissues and functions as a molecular complex providing proper environments necessary for cell development, differentiation and metabolism. Together with collagens, proteoglycans play major constitutive roles in the extracellular matrix. We have studied the metabolic regulation of extracellular matrix, especially focusing on the catabolism of heparan sulfate proteoglycans and a degrading enzyme, heparanase, necessary for this process. We have isolated a large quantity of the enzyme from cell cultures of rat parathyroid cell line (PTr) and characterized its enzymatic properties in detail. We have determined the nucleotide sequence of the mRNA encoding heparanase. We also investigated roles of extracellular matrix degradation by heparanase in the mechanism of cancer cell invasion and metastasis, using clinical specimens of lung cancers, oral squamous cell carcinomas and esophageal squamous cell carcinomas. The major results are summarized as follow.
1. Heparanase, a specific enzyme which degrades heparan sulfate proteoglycans, was isolated and its enzymatic properties, including the substrate structural requirements were studied in detail.
2. Nucleotide sequence of the gene encoding heparanase was determined.
3. Monoclonal and polyclonal antibodies against heparanase have been prepared. Characterization of these antibodies is still under way by immunohistochemical and Western blot procedures.
4. Good correlation between the invasiveness and the production of heparanase in lung cancers, oral squamous cell carcinomas and esophageal squamous cell carcinomas has been established. Studies on roles of heparanase in the mechanism of cancer invasion are under way.
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