Trypsin-2 enhances carcinoma invasion by processing tight junctions and activating ProMT1-MMP.
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.
Institute of Dentistry, University of Helsinki, and Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, Helsinki, Finland. suvi-tuuli.vilen@helsinki.fi
Suvi-Tuuli
ST
Vilen
Juho
J
Suojanen
Fidel
F
Salas
Juha
J
Risteli
Merja
M
Ylipalosaari
Outi
O
Itkonen
Hannu
H
Koistinen
Marc
M
Baumann
Ulf-Håkan
UH
Stenman
Timo
T
Sorsa
Tuula
T
Salo
Pia
P
Nyberg
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D057167:Claudins / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism*; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014357:Trypsin / Q000235:genetics / Q000378:metabolism*; D014362:Trypsinogen / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D057167:Claudins; D011498:Protein Precursors; C064831:PRSS2 protein, human; D014362:Trypsinogen; D014357:Trypsin; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14