| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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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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