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PSA forms complexes with α1-antichymotrypsin in prostate

Authors

  • Lei Zhu,

    1. Department of Clinical Chemistry, University of Helsinki and Helsinki University Central Hospital, FIN-00014 University of Helsinki, Helsinki, Finland
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  • Sari Jäämaa,

    1. Molecular Cancer Biology Program, Biomedicum Helsinki and Haartman Institute, University of Helsinki, Helsinki, Finland
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  • Taija M. af Hällström,

    1. Molecular Cancer Biology Program, Biomedicum Helsinki and Haartman Institute, University of Helsinki, Helsinki, Finland
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  • Marikki Laiho,

    1. Molecular Cancer Biology Program, Biomedicum Helsinki and Haartman Institute, University of Helsinki, Helsinki, Finland
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  • Anna Sankila,

    1. Department of Pathology, Haartman Institute, University of Helsinki and HUSLAB, Helsinki University Central Hospital, Helsinki, Finland
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  • Stig Nordling,

    1. Department of Pathology, Haartman Institute, University of Helsinki and HUSLAB, Helsinki University Central Hospital, Helsinki, Finland
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  • Ulf-Håkan Stenman,

    1. Department of Clinical Chemistry, University of Helsinki and Helsinki University Central Hospital, FIN-00014 University of Helsinki, Helsinki, Finland
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  • Hannu Koistinen

    Corresponding author
    1. Department of Clinical Chemistry, University of Helsinki and Helsinki University Central Hospital, FIN-00014 University of Helsinki, Helsinki, Finland
    • Department of Clinical Chemistry, Biomedicum Helsinki, FIN-00014 University of Helsinki, P.O. Box 63, Helsinki, Finland.
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Abstract

BACKGROUND

PSA is the most useful prostate cancer marker. However, its levels are increased also in some non-malignant conditions. In circulation, the majority of PSA is complexed with protease inhibitors, including α1-antichymotrypsin (ACT). The proportion of the PSA-ACT complex is higher in patients with prostate cancer than in controls without cancer. The expression of ACT has been shown to be higher in prostate cancer than in benign prostatic hyperplasia. However, results regarding the extent which PSA forms complexes within the prostate and whether there are differences in complex formation between normal and malignant prostatic tissue are inconsistent and limited.

METHODS

We studied complex formation of PSA secreted by cultured human prostate tissues and in the tissue by in situ proximity ligation assay (PLA). Free, total and active PSA, and the PSA-ACT complex were determined in tissue culture media by immunoassays, immunoblotting, and chromatographic methods.

RESULTS

The majority of PSA in tissue culture medium was free and enzymatically active. However, a significant proportion (1.6 ± 0.5%) of immunoreactive PSA was found to be complexed with ACT. Complex formation was confirmed by in situ PLA, which showed more intense staining of PSA-ACT in cancers with Gleason grade 3 than in adjacent benign tissues from the same patients.

CONCLUSIONS

These results show that PSA forms complexes already within the prostate and that PSA-ACT levels are increased in moderately differentiated prostate cancer tissue. This may explain, at least partially, why the ratio of serum PSA-ACT to total PSA is increased in prostate cancer. Prostate 73: 219–226, 2013. © 2012 Wiley Periodicals, Inc.

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