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Production of soluble matriptase by human cancer cell lines and cell surface activation of its zymogen by trypsin
Author(s) -
Jin Xinlian,
Hirosaki Tomomi,
Lin ChenYong,
Dickson Robert B.,
Higashi Shouichi,
Kitamura Hitoshi,
Miyazaki Kaoru
Publication year - 2005
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20418
Subject(s) - cell culture , trypsin , cancer cell , cell , extracellular , microbiology and biotechnology , chemistry , zymogen , biology , biochemistry , cancer , enzyme , genetics
Abstract The membrane‐bound serine proteinase matriptase, which is often released from the plasma membrane of epithelial and carcinoma cells, has been implicated to play important roles in both physiological and pathological conditions. However, the regulatory mechanism of its activity is poorly understood. In the present study, we examined expression and activation state of soluble matriptase in 24 human cancer cell lines. Soluble matriptase was detected in the conditioned media from all of 5 colon and 4 breast carcinoma cell lines and 8 of 10 stomach carcinoma cell lines tested. Only two of five lung cancer cell lines released the matriptase protein into the culture media. Out of the five matriptase‐negative cell lines, two cell lines expressed the matriptase mRNA. Among 24 cancer cell lines tested, 13 cell lines secreted trypsin in an active or latent form and all of them released matriptase. Most of the 24 cell lines released a latent, single‐chain matriptase of 75 kDa as a major form, as well as low levels of complex forms of an activated two‐chain enzyme with its specific inhibitor HAI‐1. Thus, these soluble matriptases appeared to have little proteolytic activity. Treatment of stomach and colon cancer cell lines with epidermal growth factor stimulated the release of matripatase/HAI‐1 complexes. In cancer cell lines secreting active trypsin, however, matriptase was released mostly as an inhibitor‐free, two‐chain active form. Trypsin seemed to activate the membrane‐bound, latent matriptase on the cell surface. These results suggest that matriptase and trypsin cooperatively function for extracellular proteolysis. © 2005 Wiley‐Liss, Inc.