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Cancer Investigation Volume 30, 2012 - Issue 8
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CELLULAR AND MOLECULAR BIOLOGY

Trypsin-2 Enhances Carcinoma Invasion by Processing Tight Junctions and Activating ProMT1-MMP

Suvi-Tuuli VilenInstitute of Dentistry, University of Helsinki, and Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, Helsinki, Finland,Correspondence[email protected]
,
Juho SuojanenInstitute of Dentistry, University of Helsinki, and Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, Helsinki, Finland,
,
Fidel SalasDepartment of Diagnostics and Oral Medicine, Institute of Dentistry, and the Oulu Center for Cell-Matrix-Research, University of Oulu, Oulu, Finland,
,
Juha RisteliDepartment of Clinical Chemistry, Institute of Diagnostics, University of Oulu, Oulu, Finland,
,
Merja YlipalosaariDepartment of Diagnostics and Oral Medicine, Institute of Dentistry, and the Oulu Center for Cell-Matrix-Research, University of Oulu, Oulu, Finland,
,
Outi Itkonen
,
Hannu KoistinenDepartment of Clinical Chemistry, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland,
,
Marc BaumannProtein Chemistry Unit, Institute of Biomedicine, University of Helsinki, Helsinki, Finland,
,
Ulf-Håkan Stenman
,
Timo SorsaInstitute of Dentistry, University of Helsinki, and Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, Helsinki, Finland,
,
Tuula Salo
&
Pia Nyberg
 show all
Pages 583-592 | Published online: 21 Aug 2012
 
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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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