Tumor-Associated Trypsinogen-2 (Trypsinogen-2) Activates Procollagenases (MMP-1, -8, -13) and Stromelysin-1 (MMP-3) and Degrades Type I Collagen
| العنوان: | Tumor-Associated Trypsinogen-2 (Trypsinogen-2) Activates Procollagenases (MMP-1, -8, -13) and Stromelysin-1 (MMP-3) and Degrades Type I Collagen |
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| المؤلفون: | Pia Nyberg, Ulf-Håkan Stenman, Jaana Vesterinen, Otso Lindy, Annukka Paju, Mathias Stenman, Tuula Salo, Timo Sorsa, Yrjö T. Konttinen, Merja Moilanen |
| المصدر: | Biochemistry. 42:5414-5420 |
| بيانات النشر: | American Chemical Society (ACS), 2003. |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | Trypsinogen, Trypsin inhibitor, Blotting, Western, Matrix metalloproteinase, Polymerase Chain Reaction, Biochemistry, Collagen Type I, Stromelysin 1, Extracellular matrix, chemistry.chemical_compound, Matrix Metalloproteinase 13, Tumor Cells, Cultured, Humans, Trypsin, Collagenases, DNA Primers, Serine protease, Enzyme Precursors, biology, Serine Endopeptidases, Extracellular Matrix, Cell biology, Enzyme Activation, Matrix Metalloproteinase 8, chemistry, Trypsin Inhibitor, Kazal Pancreatic, Cell culture, biology.protein, Matrix Metalloproteinase 3, Matrix Metalloproteinase 1, Type I collagen |
| الوصف: | A critical step in cancer growth and metastasis is the dissolution of the extracellular matrix surrounding the malignant tumor, which leads to tumor cell invasion and dissemination. Type I collagen degradation involves the initial action of collagenolytic matrix metalloproteinases (MMP-1, -8, and -13) activated by MMP-3 (stromelysin-1). The role of interactive matrix serine proteinases (MSPs), including tumor-associated trypsinogens, has been unclear in collagenolysis. Now, we provide evidence that the major isoenzyme of human tumor-associated trypsinogens, trypsin-2, can directly activate three collagenolytic proMMPs as well as proMMP-3. These proMMP activations are inhibited by tumor-associated trypsin inhibitor (TATI). Furthermore, we demonstrate that trypsin-2 efficiently degrades native soluble type I collagen, which can be inhibited by TATI. However, cell culture studies showed that trypsin-2 transfection into the HSC-3 cell line did not result in MMP-1, -3, -8, and -13 activation but affected MMP-3 and -8 production at the protein level. These findings indicate that human trypsin-2 can be regarded as a potent tumor-associated matrix serine protease capable of being the initial activator of the collagenolytic MMP activation network as well as directly attacking type I collagen. |
| تدمد: | 1520-4995 0006-2960 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8795c667b9f5e3ca92a3cd6a439e1068Test https://doi.org/10.1021/bi020582sTest |
| رقم الانضمام: | edsair.doi.dedup.....8795c667b9f5e3ca92a3cd6a439e1068 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204995 00062960 |
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