PSA forms complexes with α1-antichymotrypsin in prostate

Lei Zhu, Sari Jäämaa, Taija M. Af Hällström, Marikki Laiho, Anna Sankila, Stig Nordling, Ulf Häkan Stenman, Hannu Koistinen

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)219-226
Number of pages8
JournalProstate
Volume73
Issue number2
DOIs
StatePublished - Jan 2013
Externally publishedYes

Fingerprint

Prostate
Prostatic Neoplasms
Ligation
Culture Media
Prostatic Hyperplasia
Protease Inhibitors
Immunoassay
Immunoblotting
Neoplasms
Staining and Labeling
Serum

Keywords

  • ACT
  • prostate cancer
  • proximity ligation
  • serpin
  • tissue culture

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

Zhu, L., Jäämaa, S., Af Hällström, T. M., Laiho, M., Sankila, A., Nordling, S., ... Koistinen, H. (2013). PSA forms complexes with α1-antichymotrypsin in prostate. Prostate, 73(2), 219-226. https://doi.org/10.1002/pros.22560

PSA forms complexes with α1-antichymotrypsin in prostate. / Zhu, Lei; Jäämaa, Sari; Af Hällström, Taija M.; Laiho, Marikki; Sankila, Anna; Nordling, Stig; Stenman, Ulf Häkan; Koistinen, Hannu.

In: Prostate, Vol. 73, No. 2, 01.2013, p. 219-226.

Research output: Contribution to journalArticle

Zhu, L, Jäämaa, S, Af Hällström, TM, Laiho, M, Sankila, A, Nordling, S, Stenman, UH & Koistinen, H 2013, 'PSA forms complexes with α1-antichymotrypsin in prostate', Prostate, vol. 73, no. 2, pp. 219-226. https://doi.org/10.1002/pros.22560
Zhu L, Jäämaa S, Af Hällström TM, Laiho M, Sankila A, Nordling S et al. PSA forms complexes with α1-antichymotrypsin in prostate. Prostate. 2013 Jan;73(2):219-226. https://doi.org/10.1002/pros.22560
Zhu, Lei ; Jäämaa, Sari ; Af Hällström, Taija M. ; Laiho, Marikki ; Sankila, Anna ; Nordling, Stig ; Stenman, Ulf Häkan ; Koistinen, Hannu. / PSA forms complexes with α1-antichymotrypsin in prostate. In: Prostate. 2013 ; Vol. 73, No. 2. pp. 219-226.
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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. {\circledC} 2012 Wiley Periodicals, Inc.",
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AU - Sankila, Anna

AU - Nordling, Stig

AU - Stenman, Ulf Häkan

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N2 - 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.

AB - 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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