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Cathepsin B and cysteine proteinase inhibitors in human lung cancer cell lines

Heidtmann, Hans-Heinrich; Salge, Ursula; Abrahamson, Magnus LU ; Bencina, Mojca; Kastelic, Lili; Kopitar-Jerala, Natasa; Turk, Vito and Lah, Tamara T (1997) In Clinical and Experimental Metastasis 15(4). p.368-381
Abstract
Cell lines derived from human squamous cell (EPCL), large cell (LCLC), and small cell lung cancer (SCLC) lines were investigated for the expression of cathepsin B (Cat B) and cysteine proteinase inhibitors (CPIs). The EPLC and LCLC lines expressed 5- to 50-fold more Cat B activity and contained more mature Cat B of M(r) 27-29 kDa (> 2.5 microg/mg total protein) than the SCLC lines (< 1.0 microg/mg total protein). The LPLC lines also secreted the highest amounts of Cat B precursor of M(r) about 46 kDa. Inhibitory activities against Cat B and papain were associated with high molecular mass (HMM) and low molecular mass (LMM) inhibitory proteins, both in cell extracts and in media. About 75% of the inhibitory activity was associated with... (More)
Cell lines derived from human squamous cell (EPCL), large cell (LCLC), and small cell lung cancer (SCLC) lines were investigated for the expression of cathepsin B (Cat B) and cysteine proteinase inhibitors (CPIs). The EPLC and LCLC lines expressed 5- to 50-fold more Cat B activity and contained more mature Cat B of M(r) 27-29 kDa (> 2.5 microg/mg total protein) than the SCLC lines (< 1.0 microg/mg total protein). The LPLC lines also secreted the highest amounts of Cat B precursor of M(r) about 46 kDa. Inhibitory activities against Cat B and papain were associated with high molecular mass (HMM) and low molecular mass (LMM) inhibitory proteins, both in cell extracts and in media. About 75% of the inhibitory activity was associated with HMM inhibitors, the majority of which were kininogens (M(r) > or = 67 kDa). The LMM inhibitors of M(r) 10-15 kDa were cystatin C and stefins A and B, which were quantitated by ELISA: stefins A and B were present in cell extracts and medium in similar concentrations (5-200 ng/10(6) cells), while 80-99% of the cystatin C was released in the medium (10-195 ng/10(6) cells). Phorbol ester (PMA), which induces protein-kinase C mediated signal transduction and enhances cellular differentiation in many non-small cell lung cancer (NSCLC) cell lines, increased intracellular Cat B activity and Cat B protein as well as its secretion in some cell lines but not in others, regardless of their histological type. PMA significantly (P < 0.049) decreased intracellular stefin A concentrations in two EPLC lines and non-significantly in two LCLC lines. PMA decreased secretion of stefin A in all EPLC lines, but not in LCLC lines, while IGF-I significantly increased stefin B secretion in both SCLC lines. These data showed that lung tumor cells produce both cysteine proteinases and cystatins. As the antagonistic molecules are regulated differently in histologically different types of lung tumor cells, it is possible that an imbalance between the proteinases and their specific inhibitors plays a role in progression of certain types of lung tumors in vivo. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cathepsin B, cystatins, kininogens, lung cancer, lung carcinoma cells, proteinase inhibitors, stefins
in
Clinical and Experimental Metastasis
volume
15
issue
4
pages
368 - 381
publisher
Springer
external identifiers
  • pmid:9219725
  • scopus:0030849275
ISSN
1573-7276
DOI
10.1023/A:1018494020001
language
English
LU publication?
yes
id
93231f0b-67be-4c2f-af82-0a436f038522 (old id 1111444)
date added to LUP
2008-07-17 13:35:09
date last changed
2017-07-30 03:41:48
@article{93231f0b-67be-4c2f-af82-0a436f038522,
  abstract     = {Cell lines derived from human squamous cell (EPCL), large cell (LCLC), and small cell lung cancer (SCLC) lines were investigated for the expression of cathepsin B (Cat B) and cysteine proteinase inhibitors (CPIs). The EPLC and LCLC lines expressed 5- to 50-fold more Cat B activity and contained more mature Cat B of M(r) 27-29 kDa (&gt; 2.5 microg/mg total protein) than the SCLC lines (&lt; 1.0 microg/mg total protein). The LPLC lines also secreted the highest amounts of Cat B precursor of M(r) about 46 kDa. Inhibitory activities against Cat B and papain were associated with high molecular mass (HMM) and low molecular mass (LMM) inhibitory proteins, both in cell extracts and in media. About 75% of the inhibitory activity was associated with HMM inhibitors, the majority of which were kininogens (M(r) &gt; or = 67 kDa). The LMM inhibitors of M(r) 10-15 kDa were cystatin C and stefins A and B, which were quantitated by ELISA: stefins A and B were present in cell extracts and medium in similar concentrations (5-200 ng/10(6) cells), while 80-99% of the cystatin C was released in the medium (10-195 ng/10(6) cells). Phorbol ester (PMA), which induces protein-kinase C mediated signal transduction and enhances cellular differentiation in many non-small cell lung cancer (NSCLC) cell lines, increased intracellular Cat B activity and Cat B protein as well as its secretion in some cell lines but not in others, regardless of their histological type. PMA significantly (P &lt; 0.049) decreased intracellular stefin A concentrations in two EPLC lines and non-significantly in two LCLC lines. PMA decreased secretion of stefin A in all EPLC lines, but not in LCLC lines, while IGF-I significantly increased stefin B secretion in both SCLC lines. These data showed that lung tumor cells produce both cysteine proteinases and cystatins. As the antagonistic molecules are regulated differently in histologically different types of lung tumor cells, it is possible that an imbalance between the proteinases and their specific inhibitors plays a role in progression of certain types of lung tumors in vivo.},
  author       = {Heidtmann, Hans-Heinrich and Salge, Ursula and Abrahamson, Magnus and Bencina, Mojca and Kastelic, Lili and Kopitar-Jerala, Natasa and Turk, Vito and Lah, Tamara T},
  issn         = {1573-7276},
  keyword      = {cathepsin B,cystatins,kininogens,lung cancer,lung carcinoma cells,proteinase inhibitors,stefins},
  language     = {eng},
  number       = {4},
  pages        = {368--381},
  publisher    = {Springer},
  series       = {Clinical and Experimental Metastasis},
  title        = {Cathepsin B and cysteine proteinase inhibitors in human lung cancer cell lines},
  url          = {http://dx.doi.org/10.1023/A:1018494020001},
  volume       = {15},
  year         = {1997},
}