2005 Fiscal Year Final Research Report Summary
Development of molecular targeting drugs for anti-metastasis and anti-drug resistance of tumor cells
| Project/Area Number |
16590067
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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 | Tokyo University of Pharmacy and Life Sciences |
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Principal Investigator |
ITO Akira Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Professor, 薬学部, 教授 (70096684)
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| Project Period (FY) |
2004 – 2005
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| Keywords | tumor / metastasis and invasion / P-glycoprotein / EMMPRIN / MMP-1 / collagenase-1 / hinge-region / nobiletin / triptolide |
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| Research Abstract |
Extracellular matrix metalloproteinase inducer (EMMPRIN)/CD147 is highly expressed on the cell surface of various tumors, and closely participates in the tumor cell invasion by augmenting matrix metalloproteinase (MMP) production. In addition to the MMP-inducible activity, the cell surface EMMPRIN binds to proMMP-1/collagenase-1 on human lung carcinoma cells and human endometrium, but the significance of EMMPRIN-MMP-1 complex has not been clarified. In the present study, we clarified that EMMPRIN bind to both proMMP-1 and active MMP-1, but not other MMPs including MMPs-2, -3, and -13 on human uterine cervical carcinoma SKG-II cells. This binding was effectively interfered by a chimera protein of which hinge region was substituted by that of MMP-13, indicating that the hinge region of MMP-1 was essential for MMP-1 binding to EMMPRIN. The proMMP-1 bound to EMMPRIN was activated by plasmin, an activator of proMMPs. When the active MMP-1 bound to cell surface of SKG-II cells via EMMPRIN, the invasive activity of cells through type I-collagen gel was enhanced as compared control and proMMP-1 bound cells. The hinge region of peptide (17 mer) of MMP-1 effectively interfered with the binding of active MMP-1 as well as proMMP-1 to SKG-II cells and their type I collagen gel invasive activity. Therefore EMMPRIN is closely participates in the cancer cell invasion by forming MMP-1-EMMPRIN complex as well as induction of proMMPs. In addition, the hinge region peptide may be a useful tool for interfering with the function of MMP-1-EMMPRIN.
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Research Products
(7 results)
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[Patent(Industrial Property Rights)] 特許権2005
Inventor(s)
伊東 晃, 石田 浩之, 今田 啓介, 佐藤 隆
Industrial Property Rights Holder
伊東 晃, 石田 浩之, 今田 啓介, 佐藤 隆, 東京薬科大学
Industrial Property Number
特願2005-3222799
Filing Date
2005-10-17
Description
「研究成果報告書概要(和文)」より
