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Trypsin-2 enhances carcinoma invasion by processing tight junctions and activating ProMT1-MMP
Suvi-Tuuli Vilen1, Juho Suojanen, Fidel Salas
1Institute of Dentistry, University of Helsinki, and Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, Helsinki, Finland. suvi-tuuli.vilen@helsinki.fi
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.
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