Abstract
Neoplasms have developed strategies to protect themselves against the complement-mediated host immunity. Invasion- and metastasis-promoting membrane type-1 (MT1) matrix metalloproteinase (MMP) is strongly associated with many metastatic cancer types. The relative importance of the individual functions of MT1-MMP in metastasis was, however, unknown. We have now determined that the expression of murine MT1-MMP in murine melanoma B16F1 cells strongly increased the number of metastatic loci in the lungs of syngeneic C57BL/6 mice. In contrast, MT1-MMP did not affect the number of metastatic loci in complement-deficient C57BL/6-C3-/- mice. Our results indicated, for the first time, that the anticomplement activity of MT1-MMP played a significant role in promoting metastasis in vivo and determined the relative importance of the anticomplement activity in the total metastatic effect of this multifunctional proteolytic enzyme. We believe that our results shed additional light on the functions of MT1-MMP in cancer and clearly make this protease a promising drug target in metastatic malignancies.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Complement C3 / deficiency
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Complement C3 / genetics
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Complement C3 / immunology*
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Complement Inactivator Proteins / genetics
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Complement Inactivator Proteins / immunology*
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Complement Inactivator Proteins / metabolism
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Fibrosarcoma / enzymology
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Fibrosarcoma / genetics
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Fibrosarcoma / immunology
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Humans
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Lung Neoplasms / enzymology
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Lung Neoplasms / immunology
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Lung Neoplasms / secondary
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Mammary Neoplasms, Experimental / enzymology
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Mammary Neoplasms, Experimental / genetics
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Mammary Neoplasms, Experimental / immunology
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Mammary Neoplasms, Experimental / pathology
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Matrix Metalloproteinase 14
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Matrix Metalloproteinases / genetics
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Matrix Metalloproteinases / immunology*
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Matrix Metalloproteinases / metabolism
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Matrix Metalloproteinases, Membrane-Associated
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Melanoma, Experimental / enzymology
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Melanoma, Experimental / genetics
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Melanoma, Experimental / immunology
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Melanoma, Experimental / secondary
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Mice
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Mice, Inbred C57BL
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Neoplasms, Experimental / enzymology*
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Neoplasms, Experimental / genetics
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Neoplasms, Experimental / immunology*
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Neoplasms, Experimental / pathology
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Transfection
Substances
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Complement C3
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Complement Inactivator Proteins
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Mmp14 protein, mouse
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Matrix Metalloproteinases
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Matrix Metalloproteinases, Membrane-Associated
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Matrix Metalloproteinase 14