Journal
EXPERIMENTAL CELL RESEARCH
Volume 314, Issue 4, Pages 914-926Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2007.10.025
Keywords
enterokinase; intracellular vesicle; MMP-9; oral carcinoma; proteolysis; trypsin-2
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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 colocalized 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. (C) 2007 Elsevier Inc. All rights reserved.
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