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Regulation of the enzymatic activity of prostate-specific antigen and its reactions with extracellular protease inhibitors in prostate cancer

Lilja, H. LU orcid (1995) In Scandinavian Journal of Clinical and Laboratory Investigation, Supplement 55(220). p.47-56
Abstract

Prostate-specific antigen (PSA) is a tissue-specific serine protease similar in structure to the trypsin-like glandular kallikreins but which is unique inasmuch as the enzyme activity is similar to that of chymotrypsin. The active enzyme is a single chain glycoprotein of 237 amino acids. The major form of PSA in serum is complexed to α1-antichymotrypsin (ACT). A small amount is free, non-complexed despite a large excess of ACT. This suggests that the form in serum lacks enzyme activity. Although serum PSA concentrations are regularly abnormally high (above 4 μg/L) in prostate cancer (CAP), the utility of PSA measurements in the early detection of CAP is limited, as many tumors are undetected at a cut-off of 4 μg/L. Also, 25%... (More)

Prostate-specific antigen (PSA) is a tissue-specific serine protease similar in structure to the trypsin-like glandular kallikreins but which is unique inasmuch as the enzyme activity is similar to that of chymotrypsin. The active enzyme is a single chain glycoprotein of 237 amino acids. The major form of PSA in serum is complexed to α1-antichymotrypsin (ACT). A small amount is free, non-complexed despite a large excess of ACT. This suggests that the form in serum lacks enzyme activity. Although serum PSA concentrations are regularly abnormally high (above 4 μg/L) in prostate cancer (CAP), the utility of PSA measurements in the early detection of CAP is limited, as many tumors are undetected at a cut-off of 4 μg/L. Also, 25% of all men with benign prostate hyperplasia (BPH) have serum PSA levels above 4 μg/L. Using assays specially developed to measure free and complexed forms of PSA in serum, we found the proportion of PSA-ACT complexes to be higher in CAP than in BPH, but the ratio of free-to-total PSA in serum to be lower. Using an abnormally low ratio of free-to-total PSA to detect CAP increases diagnostic specificity by 15 to 20%, compared to using a high serum PSA concentration. This suggests that the ratios of free-to-total PSA significantly increase the ability to distinguish BPH from localized CAP. The molecular basis is unclear, but may be related to the high incidence of prostate tumor cells producing both PSA and ACT. This is in contrast to the lack of ACT production in BPH epithelium. Possibly owing to lack of ACT production in BPH areas, conditions are not optimal for complex formation, whereas tumors producing both ACT and PSA may promote the formation of PSA-ACT complexes in CAP.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
α-macroglobulin, Alpha--antichymotrypsin, Benign prostate hyperplasia, Immunoassays, Kallikreins, Protein C inhibitor, Serine proteases, Serpins
in
Scandinavian Journal of Clinical and Laboratory Investigation, Supplement
volume
55
issue
220
pages
10 pages
publisher
Taylor & Francis
external identifiers
  • scopus:0028912668
  • pmid:7544478
ISSN
0085-591X
language
English
LU publication?
yes
id
81a03117-3f76-4f12-978d-00e03f627619
date added to LUP
2022-12-08 13:13:27
date last changed
2024-01-02 13:55:51
@article{81a03117-3f76-4f12-978d-00e03f627619,
  abstract     = {{<p>Prostate-specific antigen (PSA) is a tissue-specific serine protease similar in structure to the trypsin-like glandular kallikreins but which is unique inasmuch as the enzyme activity is similar to that of chymotrypsin. The active enzyme is a single chain glycoprotein of 237 amino acids. The major form of PSA in serum is complexed to α<sub>1</sub>-antichymotrypsin (ACT). A small amount is free, non-complexed despite a large excess of ACT. This suggests that the form in serum lacks enzyme activity. Although serum PSA concentrations are regularly abnormally high (above 4 μg/L) in prostate cancer (CAP), the utility of PSA measurements in the early detection of CAP is limited, as many tumors are undetected at a cut-off of 4 μg/L. Also, 25% of all men with benign prostate hyperplasia (BPH) have serum PSA levels above 4 μg/L. Using assays specially developed to measure free and complexed forms of PSA in serum, we found the proportion of PSA-ACT complexes to be higher in CAP than in BPH, but the ratio of free-to-total PSA in serum to be lower. Using an abnormally low ratio of free-to-total PSA to detect CAP increases diagnostic specificity by 15 to 20%, compared to using a high serum PSA concentration. This suggests that the ratios of free-to-total PSA significantly increase the ability to distinguish BPH from localized CAP. The molecular basis is unclear, but may be related to the high incidence of prostate tumor cells producing both PSA and ACT. This is in contrast to the lack of ACT production in BPH epithelium. Possibly owing to lack of ACT production in BPH areas, conditions are not optimal for complex formation, whereas tumors producing both ACT and PSA may promote the formation of PSA-ACT complexes in CAP.</p>}},
  author       = {{Lilja, H.}},
  issn         = {{0085-591X}},
  keywords     = {{α-macroglobulin; Alpha--antichymotrypsin; Benign prostate hyperplasia; Immunoassays; Kallikreins; Protein C inhibitor; Serine proteases; Serpins}},
  language     = {{eng}},
  number       = {{220}},
  pages        = {{47--56}},
  publisher    = {{Taylor & Francis}},
  series       = {{Scandinavian Journal of Clinical and Laboratory Investigation, Supplement}},
  title        = {{Regulation of the enzymatic activity of prostate-specific antigen and its reactions with extracellular protease inhibitors in prostate cancer}},
  volume       = {{55}},
  year         = {{1995}},
}