Activation of type IV procollagenases by human tumor-associated trypsin-2

Sorsa T, Salo T, Koivunen E, Tyynela J, Konttinen YT, Bergmann U, Tuuttila A, Niemi E, Teronen O, Heikkila P, Tschesche H, et al. (1997)
JOURNAL OF BIOLOGICAL CHEMISTRY 272(34): 21067-21074.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Sorsa, T; Salo, T; Koivunen, E; Tyynela, J; Konttinen, YT; Bergmann, U; Tuuttila, A; Niemi, E; Teronen, O; Heikkila, P; Tschesche, HaraldUniBi; Leinonen, J
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Abstract / Bemerkung
Increased production of proteinases, such as matrix metalloproteinases (MMPs), is a characteristic feature of malignant tumors. Some human cancers :Ind cell lines derived from them also express trypsinogen, but the function of the extrapancreatic trypsin has remained unclear, In this study we cloned and sequenced trypsinogen-a cDNA from human COLO 205 colon carcinoma cells and characterized the ability of the enzyme to activate latent human type TV procollagenases (proMMP-2 and proMMP-9). As shown by cloning and N-terminal amino acid sequencing, the amino acid sequence of tumor associated trypsin-a is identical to that of pancreatic trypsin-a. We found that both pancreatic trypsin-a and tumor cell-derived trypsin-a are efficient activators of proMMP-9 and are capable of activating proMMP-9 at a molar ratio of 1:1000, the lowest reported so far. Human trypsin-a was a more efficient activator than widely used bovine trypsin and converted the 92-kDa proMMP-9 to a single 77-kDa product that was not fragmented further. The single peptide bond cleaved by trypsin-a in proMMP-9 was Arg(87)-Phe(88), The generation of the 77-kDa species coincided with the increase in specific activity of MMP-9. In contrast, trypsin-2 only partially activated proMMP-2. Trypsin-a cleaved the Arg(99)-Lys(100) peptide bond of proMMP-2 generating 62-65-kDa MMP-2 species. Trypsin-a-induced proMMP-2 and -9 conversions were inhibited by tumor-associated trypsin inhibitor added either prior to or during activation indicating that proMMPs were not activated autocatalytically. Trypsin-2 also activated proMMPs associated with tissue inhibitor of matrix metalloproteinases, the complexes of which are thought to be the major MMP forms in vivo. The ability of human tumor cell-derived trypsin-a to activate latent MMPs suggests a role fbr trypsin-a in initiating the proteinase cascade that mediates tumor invasion and metastasis formation.
Erscheinungsjahr
1997
Zeitschriftentitel
JOURNAL OF BIOLOGICAL CHEMISTRY
Band
272
Ausgabe
34
Seite(n)
21067-21074
ISSN
0021-9258
Page URI
https://pub.uni-bielefeld.de/record/1627649

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Sorsa T, Salo T, Koivunen E, et al. Activation of type IV procollagenases by human tumor-associated trypsin-2. JOURNAL OF BIOLOGICAL CHEMISTRY. 1997;272(34):21067-21074.
Sorsa, T., Salo, T., Koivunen, E., Tyynela, J., Konttinen, Y. T., Bergmann, U., Tuuttila, A., et al. (1997). Activation of type IV procollagenases by human tumor-associated trypsin-2. JOURNAL OF BIOLOGICAL CHEMISTRY, 272(34), 21067-21074. https://doi.org/10.1074/jbc.272.34.21067
Sorsa, T., Salo, T., Koivunen, E., Tyynela, J., Konttinen, Y. T., Bergmann, U., Tuuttila, A., Niemi, E., Teronen, O., Heikkila, P., et al. (1997). Activation of type IV procollagenases by human tumor-associated trypsin-2. JOURNAL OF BIOLOGICAL CHEMISTRY 272, 21067-21074.
Sorsa, T., et al., 1997. Activation of type IV procollagenases by human tumor-associated trypsin-2. JOURNAL OF BIOLOGICAL CHEMISTRY, 272(34), p 21067-21074.
T. Sorsa, et al., “Activation of type IV procollagenases by human tumor-associated trypsin-2”, JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 272, 1997, pp. 21067-21074.
Sorsa, T., Salo, T., Koivunen, E., Tyynela, J., Konttinen, Y.T., Bergmann, U., Tuuttila, A., Niemi, E., Teronen, O., Heikkila, P., Tschesche, H., Leinonen, J., Osman, S., Stenman, U.H.: Activation of type IV procollagenases by human tumor-associated trypsin-2. JOURNAL OF BIOLOGICAL CHEMISTRY. 272, 21067-21074 (1997).
Sorsa, T, Salo, T, Koivunen, E, Tyynela, J, Konttinen, YT, Bergmann, U, Tuuttila, A, Niemi, E, Teronen, O, Heikkila, P, Tschesche, Harald, Leinonen, J, Osman, S, and Stenman, UH. “Activation of type IV procollagenases by human tumor-associated trypsin-2”. JOURNAL OF BIOLOGICAL CHEMISTRY 272.34 (1997): 21067-21074.

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