Activation of macrophages by mucins produced from epithelial cancer cells and its effect
| Project/Area Number |
12672134
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto Sangyo University |
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Principal Investigator |
NAKADA Hiroshi Kyoto Sangyo University, Engineering, Professor, 工学部, 教授 (90113141)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | mucincyclooxyganase 2 / macrophage / prostaglandin E2 / cyclooxyganase 2 / プロスタグランジンE_2 / プロスタグランジンE2(PGE2) / シクロオキシゲナーゼ2(COX-2) / スカベンジャーリセプター |
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| Research Abstract |
We found that mucins produced by epithelial cancer cells activated monocytes/macrophages. Monocytes incubated with mucins produced cytokines such as IL-1β and PGE2, which synthesis was elevated in a dose-dependent manner. Cyclooxygenase 2 (COX2) is a rate-limiting enzyme for biosynthesis of PGE2. It is noted that COX2 mRNA and enzyme protein were induced by mucins. We also examined immunohistochemically the localization of COX2 protein and mucins in human colorectal cancer tissues. It is noteworthy that COX2-expressing macrophages were located around the region in which mucins were detectable.
Next, we examined the formation of cancer tissues using a mouse mammary tumor cell line, TA3-Ha and TA3-St. It is known that the former produces mucins named epiglycanin, but the latter does not. Although both cells grew at the similar rate in vitro, the former formed the cancer tissues much more rapidly than the latter in vivo. Induction of COX2 of infiltrated macrophages could be observed in the former tissues immunohistochemically but not in the latter. These results indicate that the induction of COX2 by mucins plays a significant role in the tumor formation.
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Report
(4 results)
Research Products
(19 results)
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[Publications] Oshinaga, E., Bay, S., Tello, D., Babino, A., Pritsch, O., Assemat, K., Cantacuzene, D., Nakada, H. and Alzari, P.: "Analysis of the fine specificity of Tn-binding proteins using synthetic glycopeptide epitopes and a biosensor based on surface plamson resonance spectroscopy"FEBS Lett.. 469. 24-28 (2000)
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[Publications] Guerre, S.V., Lo-Man, R., Bay, S., Deriaud, E., Nakada, H., Leclerc, C. and Cantacuzene, D.: "Short synthetic glycopeptides successfully induce antibody responses to carcinoma-associated Tn antigen"J. Peptide Res.. 55. 173-180 (2000)
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[Publications] Inoue, M., Takahashi, S., Yamashina, I., Kaibori, M., Okumura, T., Kamiyama, Y., Vichier-Guerre, S., Cantacuzene, D. and Nakada, H.: "High density O-glycosylation of the MUC2 tandem repeat unit by N-acetylgalactosaminyltransferase-3 in colonic adenocarcinoma extracts"Cancer Res.. 61. 950-956 (2001)
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[Publications] Akita, K., Fushiki, S., Fujimoto, T., Inoue, M., Oguri, K., Okayama, M., Yamashina, I. and Nakada, H.: "Developmental expression of a unique carbohydrate antigen, Tn antigen, in mouse central nervous tissues"J. Neurosci. Res.. 65. 595-603 (2001)
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[Publications] Inaba, T., Sano, H., Kawahito, Y., Hla, T., Akita, K., Toda, M., Yamashina, L., Inoue, M. and Nakada, H.: "Induction of cyclooxygenase-2 in monocyte/macrophage by inucins secreted from colon cancer cells"Proc. Natl. Acad. Sci. USA. 100. 2736-2741 (2003)
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