Abstract
Enhanced proteolysis and altered tight junction (TJ) proteins associate with carcinoma invasion. We hypothesized that trypsin-2, a tumor-associated serine proteinase, induces tongue carcinoma invasion by activating pro-membrane type-1 matrix metalloproteinase (MT1-MMP) and disturbing the TJs. The effects of invasion were analyzed using trypsin-2 over-expressing human tongue squamous cell carcinoma cells (Try2-HSC-3) in vitro and in vivo. The invasion of Try2-HSC-3 cells was increased in mouse xenografts and human organotypic model. Trypsin-2 activated proMT1-MMP, as well as altered the expression of TJ protein claudin-7. In conclusion, trypsin-2 over-expression enhanced tongue carcinoma cell invasion by various genetic and proteolytic mechanisms.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carcinoma, Squamous Cell / genetics
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Carcinoma, Squamous Cell / metabolism*
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Carcinoma, Squamous Cell / pathology*
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Cell Line, Tumor
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Cell Movement / genetics
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Claudins / genetics
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Claudins / metabolism
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Enzyme Activation
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Female
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Gene Expression
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Gene Expression Profiling
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Humans
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Matrix Metalloproteinase 14 / metabolism*
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Mice
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Mice, Nude
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Neoplasm Invasiveness
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Protein Precursors / genetics
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Protein Precursors / metabolism*
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Tight Junctions / metabolism*
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Tongue Neoplasms / genetics
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Tongue Neoplasms / metabolism*
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Tongue Neoplasms / pathology*
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Trypsin / genetics
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Trypsin / metabolism*
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Trypsinogen / genetics
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Trypsinogen / metabolism*
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Tumor Burden / genetics
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Xenograft Model Antitumor Assays
Substances
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Claudins
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Protein Precursors
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PRSS2 protein, human
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Trypsinogen
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Trypsin
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MMP14 protein, human
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Matrix Metalloproteinase 14