title: Production of soluble matriptase by human cancer cell lines and cell surface activation of its zymogen by trypsin.
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.
authors.affiliation: Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, 641-12 Maioka-cho, Totsuka-ku, Yokohama 244-0813, Japan.
authors.forename: Xinlian
authors.initials: X
authors.lastname: Jin
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hirosaki
authors.forename: Chen-Yong
authors.initials: CY
authors.lastname: Lin
authors.forename: Robert B
authors.initials: RB
authors.lastname: Dickson
authors.forename: Shouichi
authors.initials: S
authors.lastname: Higashi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kitamura
authors.forename: Kaoru
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D045744:Cell Line, Tumor; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D014357:Trypsin / Q000378:metabolism*
chemical_list: D004792:Enzyme Precursors; D012697:Serine Endopeptidases; C485595:matriptase; D014357:Trypsin