PSA forms complexes with α1-antichymotrypsin in prostate.
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 α(1) -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.
Department of Clinical Chemistry, University of Helsinki and Helsinki University Central Hospital, FIN-00014 University of Helsinki, Helsinki, Finland.
Lei
L
Zhu
Sari
S
Jäämaa
Taija M
TM
Af Hällström
Marikki
M
Laiho
Anna
A
Sankila
Stig
S
Nordling
Ulf-Håkan
UH
Stenman
Hannu
H
Koistinen
D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000378:metabolism; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism*
D046912:Multiprotein Complexes; D000514:alpha 1-Antichymotrypsin; D017430:Prostate-Specific Antigen