1995 Fiscal Year Final Research Report Summary
Cancer Associated Carbohydrate Antigens Expressed On Mucin-type Glycoproteins
| Project/Area Number |
06672211
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | kyoto Sangyo Uni. |
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Principal Investigator |
NAKADA Hiroshi Kyoto Sangyo Uni. Biotechnology Professor, 工学部・生物工学科, 教授 (90113141)
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| Project Period (FY) |
1994 – 1995
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| Keywords | E-selectin / Sialyl-LeA antigen / Mucin / 癌関連糖鎖抗原 / 単クローン抗体 |
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| Research Abstract |
Novel glycoproteins carrying sialyl-LeA antigens (SL-GP) were isolated from ascites fluid from a patient with colorectal cancer by immunoaffinity chromatography. SL-GP showed a typical mucin type amino acid composition in which Ser, Thr Pro together accounted for greater than 50 % of the total amino acid residues. A large amount of carbohydrate (about 80 %) was present in SL-GP.The number of O-glycans carrying sialyl-LeA antigens comprised about 9 % of the total number of O-glycosidic chains. SL-GP could bind to IL-1 treated HUVECs, and the binding was inhibited by anti-E-selectin and anti-sialyl-LeA monoclonal antibodies. The binding of colorectal cancer cells, LS180, to HUVECs was assayd in the presence of SL-GP,oligosaccharides prepared from SL-GP and human milk Sialyl-LeA hexasaccharide. SL-GP inhibited most effectively, whereas equivalent amounts of the SL-GP oligosaccharides and milk sialyl-LeA hexasaccharide inhibited it slightly. These results constitute direct evidence that a unique arrangement of sialyl-LeA antigens on the polypeptide chain, probably a cluster, is essential for the binding of E-selectin.
To examine the modification of E-selectin caused by ligation, HUVECs were metabolically labeled with ^<32> P-phosphate. Phosphorylation at serine residue of E-selectin was demonstrated and ligation with SL-GP elevated the phosphorylation, which might have led to the activation of E-selectin metabolism. To further investigate the effect of SL-GP on the metabolic behavior of E-selectin, pulse-chase experiments were performed. While pulse-labeling of E-selectin in the presence of SL-GP indicated that the degradation of E-selectin was induced by SL-GP ligation, labeling after pre-ligation with SL-GP revealed an increase in the synthesis of E-selectin. The synthesis may reflect compensation for the E-selectin degraded on pre-ligation, resulting in prolonged expression of E-selectin.
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Research Products
(13 results)
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[Publications] Ohsio, G., Yoshioka, H., Manabe, T., Sakahara, H., Yamabe, H., Imamura, M., Inoue, M., Tanaka, N., Nakada, H., & Yamashina, I.: "Expression of sialosyl-Tn antigen (monoclonal antibody MLS102 reactive) in normal tissues and malignant tumors of the digestive tract" J.Cancer Res.Clin.Oncol.120. 325-330 (1994)
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「研究成果報告書概要(欧文)」より
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[Publications] Ohshio, G., Imamura, T., Imamura, M., Yamabe, H., Sakahara, H., Nakada, H., & Yamashina, I.: "Distribution of Tn antigen recognized by an anti-Tn monoclonal antibody (MLS128) in normal and malignant tissues of the digestive tract" J.Cancer Res.Clin.Oncol.121. 247-252 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Yao, Z., Sakahara, H., Zhang, M., Kobayashi, H., Nakada, H., Yamashina, I., & Konishi, J.: "Radioimmunoimaging of colon cancer xenografts with anti-Tn monoclonal antibody" Nucl.Med.Biol.22. 199-203 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Yao, Z., Zhang, M., Kobayashi, Hj., Sakahara, H., Nakada, H., Yamashina, I., & Konishi, J.: "Improved targeting of radiolabeled streptavidin in tumors pretargeted with biotinylated monoclonal antibodies through an avidin chase" J.Nucl.Med.36. 837-841 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Sakahara, H., Onodera, H., Shirato, M., Yao, Z., Ohshio, G., Kobayashi, H., Hosono, M., Yano, S., Nakada, H., Imamura, M., Yamashina, I., & Konishi, J.: "Immunoscintigraphy of colorectal cancer using ^<111>Inlabeled monoclonal antibody to mucin" Cancer Immunol.Immunother. 41. 157-161 (1995)
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「研究成果報告書概要(欧文)」より
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