A potentially novel peptidase, resembling but distinct from neutrophil elastase, produced by carcinoma cells.
Neutrophil elastase (NE) is the only neutral protease that can degrade broad substrates of extracellular matrix components. In the present study, we describe the NE-like molecule expressed in many carcinoma cells, which has similar activity to NE and pancreatic elastase, but is immunologically different from NE, and is not inhibited by NE or pancreatic elastase inhibitor at all. Intracellular activity of NE or pancreatic elastase and immunological reactivity of NE in ten carcinoma cell lines and freshly purified neutrophils were measured by CellProbe and enzyme immunoassay, respectively. The NE and pancreatic inhibitory effect to the extracts of the ten cell lines was further examined using NE and pancreatic elastase inhibitor (ONO-5046.Na). Only two carcinoma cell lines out of ten had low immunoreactive NE, whereas neutrophils had high immunoreactivity in the extract. Flow cytometric analyses demonstrated that five out of 11 carcinoma cell lines had a high degrading activity of Ala-Ala-Pro-Val site in more than half of the population. SUIT-2 had the highest activity, but had no immunoreactivity for NE. Furthermore, the NE-like activity in the SUIT-2 cells was not inhibited by ONO-5046.Na. The present study demonstrated the NE-like molecule expressed in many types of carcinoma cells, which is potentially a new and specific protease produced by cancer cells. It would be of great interest to identify this NE-like molecule specific to the tumor, leading to a possible promising treatment of advanced carcinomas.
Yamaguchi
K
K
Department of Surgery II, Kumamoto University School of Medicine, Kumamoto 860-8556, Japan.
Shimada
S
S
Tashima
S
S
Ogawa
M
M
D002277:Carcinoma / Q000201:enzymology*; D005434:Flow Cytometry; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology; D010447:Peptide Hydrolases / Q000276:immunology / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013379:Substrate Specificity; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D010447:Peptide Hydrolases; D019272:Leukocyte Elastase; D005998:Glycine