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Intracellular co-localization of trypsin-2 and matrix metalloprotease-9: Possible proteolytic cascade of trypsin-2, MMP-9 and enterokinase in carcinoma

Vilen, ST; Nyberg, P; Hukkanen, M; Sutinen, M; Ylipalosaari, M; Bjartell, Anders LU ; Paju, A; Haaparanta, V; Stenman, UH and Sorsa, T, et al. (2008) In Experimental Cell Research 314(4). p.914-926
Abstract
Tumor-associated trypsin-2 and matrix metalloprotease-9 (MMP-9) are associated with cancer, particularly with invasive squamous cell carcinomas. They require activation for catalytical competence via proteolytic cascades. One cascade is formed by enterokinase, trypsin-2 and MMP-9; enterokinase activates trypsinogen-2 to trypsin-2, which is an efficient proMMP-9 activator. We describe here that oral squamous cell carcinomas express all members of this cascade: MMP-9, trypsin-2 and enterokinase. The expression of enterokinase in a carcinoma cell line not derived from the duodenum was shown here for the first time. Enterokinase directly cleaved proMMP-9 at the Lys(65)-Ser(66) site, but failed to activate it in vitro. We demonstrated by... (More)
Tumor-associated trypsin-2 and matrix metalloprotease-9 (MMP-9) are associated with cancer, particularly with invasive squamous cell carcinomas. They require activation for catalytical competence via proteolytic cascades. One cascade is formed by enterokinase, trypsin-2 and MMP-9; enterokinase activates trypsinogen-2 to trypsin-2, which is an efficient proMMP-9 activator. We describe here that oral squamous cell carcinomas express all members of this cascade: MMP-9, trypsin-2 and enterokinase. The expression of enterokinase in a carcinoma cell line not derived from the duodenum was shown here for the first time. Enterokinase directly cleaved proMMP-9 at the Lys(65)-Ser(66) site, but failed to activate it in vitro. We demonstrated by confocal microscopy that MMP-9 and trypsin-2 co-localized in intracellular vesicles of the carcinoma cells. This co-localization of trypsin-2 and MMP-9 resulted in intracellular proMMP-9 processing that represented fully or partially activated MMP-9. However, although both proteases were present also in various bone tumor tissues, MMP-9 and trypsin-2 never co-localized at the cellular level in these tissues. This suggests that the intracellular vesicular co-localization, storage and possible activation of these proteases may be a unique feature for aggressive epithelial tumors, such as squamous cell carcinomas, but not for tumors of mesenchymal origin. (Less)
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Contribution to journal
publication status
published
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Experimental Cell Research
volume
314
issue
4
pages
914 - 926
publisher
Academic Press
external identifiers
  • pmid:18062964
  • wos:000253405900023
  • scopus:38949121712
ISSN
1090-2422
DOI
10.1016/j.yexcr.2007.10.025
language
English
LU publication?
yes
id
61c1d29c-c302-4c0b-bf7b-9f74bc9059ad (old id 1143533)
date added to LUP
2008-07-29 15:00:29
date last changed
2017-01-01 05:11:33
@article{61c1d29c-c302-4c0b-bf7b-9f74bc9059ad,
  abstract     = {Tumor-associated trypsin-2 and matrix metalloprotease-9 (MMP-9) are associated with cancer, particularly with invasive squamous cell carcinomas. They require activation for catalytical competence via proteolytic cascades. One cascade is formed by enterokinase, trypsin-2 and MMP-9; enterokinase activates trypsinogen-2 to trypsin-2, which is an efficient proMMP-9 activator. We describe here that oral squamous cell carcinomas express all members of this cascade: MMP-9, trypsin-2 and enterokinase. The expression of enterokinase in a carcinoma cell line not derived from the duodenum was shown here for the first time. Enterokinase directly cleaved proMMP-9 at the Lys(65)-Ser(66) site, but failed to activate it in vitro. We demonstrated by confocal microscopy that MMP-9 and trypsin-2 co-localized in intracellular vesicles of the carcinoma cells. This co-localization of trypsin-2 and MMP-9 resulted in intracellular proMMP-9 processing that represented fully or partially activated MMP-9. However, although both proteases were present also in various bone tumor tissues, MMP-9 and trypsin-2 never co-localized at the cellular level in these tissues. This suggests that the intracellular vesicular co-localization, storage and possible activation of these proteases may be a unique feature for aggressive epithelial tumors, such as squamous cell carcinomas, but not for tumors of mesenchymal origin.},
  author       = {Vilen, ST and Nyberg, P and Hukkanen, M and Sutinen, M and Ylipalosaari, M and Bjartell, Anders and Paju, A and Haaparanta, V and Stenman, UH and Sorsa, T and Salo, T},
  issn         = {1090-2422},
  language     = {eng},
  number       = {4},
  pages        = {914--926},
  publisher    = {Academic Press},
  series       = {Experimental Cell Research},
  title        = {Intracellular co-localization of trypsin-2 and matrix metalloprotease-9: Possible proteolytic cascade of trypsin-2, MMP-9 and enterokinase in carcinoma},
  url          = {http://dx.doi.org/10.1016/j.yexcr.2007.10.025},
  volume       = {314},
  year         = {2008},
}