1997 Fiscal Year Final Research Report Summary
ROLES OF MEMBRANE TYPE MATRIX METALLOPROTEINASE IN BREAST TUMOR METASTASIS
| Project/Area Number |
07044240
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Experimental pathology
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| Research Institution | UNIVERSITY OF TOKYO (1997)
Kanazawa University (1995-1996) |
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Principal Investigator |
SEIKI Motoharu UNIVERSITY OF TOKYO,INSTITUTE OF MEDICAL SCIENCE,PROFESSOR, 医科学研究所, 教授 (10154634)
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| Co-Investigator(Kenkyū-buntansha) |
トンプソン エリク ジョージタウン大学, 癌研究所, 準教授
ゴールドバーグ グレゴリ ワシントン大学, 医学部, 教授
OKADA Akiko UNIVERSITY OF TOKYO,INSTITUTE OF MEDICAL SCIENCE,ASSISTANT PROFESSOR, 医科学研究所, 助手 (00233320)
SATO Hiroshi KANAZAWA UNIVERSITY,CANCER RESEARCH INSTITUTE,ASSOCIATE PROFESSOR, がん研究所, 助教授 (00115239)
GOLDBERG Glegory.I. WASHINGTON UNIVERSITY SCHOOL OF MEDICINE,PROFESSOR
THOMPSON Erik.W. GEORGETOWN UNIVERSITY,CANCER INSTITUTE,ASSOCIATE PROFESSOR
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| Project Period (FY) |
1995 – 1997
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| Keywords | CANCER / INVASON AND METASTASIS / BREAST CARCINOMA / MATRIX METALLOPROTEINASE |
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| Research Abstract |
Gelatinase A (GelA) is believed to be important for cancer cell invasion and metastasis. Gelatinase A is produced as an inactive proenzyme (proGelA) and activated by a cell surface activator on cancer cells. We identified membrane-type 1 matrix metalloproteinase as a possible cell surface activator in 1994 and have extended the study to elucidate its relevance to cancer including breast carcinomas. During the three years we obtained the following results supported by the grant.
1. MT1-MMP expression was demonstrated in various types of human cancers such as breast, gastric, colon, head and neck, and nasophagial carcinomas.
2. Expression of MT1-MMP in carcinomas correlated well to the activation of GelA in the tissue suggesting that MT1-MMP is surely the GelA activator in cancers.
3. Immunohistochmistry localized both MT1-MMP and gelatinase A to the cancer cells and also surrounding stromal fibroblasts.
4. However carcinoma cells did not express GelA but it was expressed in the surrounding fibroblasts.
5. MT1-MMP was shown to bind proGelA by using TIMP-2 as a adapter. Thus Three molecular complex is thought to be formed on cancer cell surface. ProGelA in the complex is thought to be activated by the neighboring free MT1- MMP.
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[Publications] Sato, H., Tanaka, M., Takino, T., Inoue, M.& Seiki, M.: "Assignment of the Human Genes for Membrane-Type-1, -2 and -3 Matrix Metalloproteinases to 14q12.2,16q12.2-21 and 8q21, Respectively by in Situ Hybridization." Genomics. 39. 412-413 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Pulyaeva, H., Bueno, J., POlette, M., Bire, baut, P., Sato, H., Seiki, M.& Thompson, E.W.: "MT1-MMP correlates with MMP-2 activation potential seen after epitherial to mesenchymal transition in human breast carcinoma cells." Clin.Exp.Metastasis. 15. 111-120 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Yu.M., Bowden, E.T., Sitlani, H., Sato, H., Seiki, M., Mueller, S.C.& Thompson, E.W.: "Tyrosin phosphorylation mediates ConA-in-duced membrane type-1 matrix metalloproteinase expression and matrix metalloproteinase-2 activation in MDA-MB-231 human breast carcinoma cells." Cancer Res.57. 5028-5032 (1997)
Description
「研究成果報告書概要(欧文)」より
