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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

In English

Författare

  • ST Vilen
  • P Nyberg
  • M Hukkanen
  • M Sutinen
  • M Ylipalosaari
  • Anders Bjartell
  • A Paju
  • V Haaparanta
  • UH Stenman
  • T Sorsa
  • T Salo
Visa allt

Summary, in English

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.

Publiceringsår

2008

Språk

Engelska

Sidor

914-926

Publikation/Tidskrift/Serie

Experimental Cell Research

Volym

314

Issue

4

Dokumenttyp

Artikel i tidskrift

Förlag

Academic Press

Ämne

  • Clinical Medicine
  • Cancer and Oncology

Aktiv

Published

Forskningsgrupp

  • Urological cancer, Malmö

ISBN/ISSN/Övrigt

  • ISSN: 1090-2422