Prostate-specific antigen in serum occurs predominantly in complex with alpha 1-antichymotrypsin

Lilja, Hans; Christensson, Anders; Dahlén, Ulrika; Matikainen, M; Nilsson, Olle; Pettersson, Kim; Lövgren, Timo

doi:10.1093/clinchem/37.9.1618

Cited by 855 publications

(251 citation statements)

References 13 publications

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“…A polyclonal rabbit IgG against native PCI, produced as described previously [ 151, was used in an immunoradiometric assay. The production and characterization of murine monoclonal antibodies (mAb) against PSA (2E9 and 2Hll) and PCI (Mll-5 and M1-12) have been reported previously [33,341. We immobilized mAb 2E9 on Affi-Gel (1 mglml), according to manufacturer's instructions, for affinity chromatography.…”

Section: Antibodiesmentioning

confidence: 99%

“…For the measurement of PCI-PSA complexes in biological fluids, a sensitive IFMA was developed, similar to previously described methods [33]. 1 pg mAb anti-PCI (M11-5) in each well served as the trapping antibody that identifies different forms of PCI; native, modified and PCI in complex with activated protein C and plasma kallikrein [34].…”

Section: Ifma For Pci-psa Complexesmentioning

confidence: 99%

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Complex formation between protein C inhibitor and prostate‐specific antigen in vitro and in human semen

Christensson

Lilja

1994

European Journal of Biochemistry

170

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Protein C inhibitor (PCI), a serine-proteinase inhibitor first purified from human blood plasma, occurs at high concentrations (3-4 pM) in seminal fluid in both a high-molecular-mass and lowmolecular-mass form. Immunochemical data have previously suggested that PCI in seminal plasma forms complexes with the most abundant serine proteinase in semen, prostate-specific antigen (PSA). To provide a structural characterization of the PCI target, immunodetected as PSA, a procedure was developed to isolate low-molecular-mass and high-molecular-mass-forms of PCI from seminal fluid. The high-molecular-mass form of PCI, recognized by monoclonal antibodies against PSA, was dissociated by alkaline treatment into the low-molecular-mass form of PCI and a 33-kDa protein identified as PSA by 25 conclusive steps of N-terminal sequence analysis. We developed a sensitive immunofluorometric assay (IFMA) to measure PCI-PSA complexes in body fluids and investigated the rate at which purified PSA may form complexes with purified PCI. Formation of complexes detected by this IFMA and the appearance of SDS-stable approximately 90-kDa complexes paralleled loss of PSA activity recorded with chromogenic substrates. The rate of complex formation was slow compared to that reported for PCI and activated protein C, but was enhanced up to sixfold in the presence of heparin. Less than 10% of the initial PSA activity remained after 3 h incubation with a sevenfold molar excess of PCI and in the presence of heparin.In freshly collected ejaculates, the rate of PCI-PSA complex formation measured by IFMA was similar to that observed between the purified proteins, and paralleled the appearance of SDS-stable complexes by immunoblotting. During gel dissolution in freshly collected ejaculates, approximately 40% of immunodetected PCI becomes complexed to PSA. Although PCI is a slow inhibitor of PSA, complexes between PCI and PSA are detected at levels that correspond to an inactivation of up to 5% of the PSA activity in the ejaculate.Human protein C inhibitor (PCI), a 57-kDa single-chain glycoprotein with inhibitory activity against serine proteinases, was first, identified and characterized from human blood plasma [ l , 21. PCI is a slow inhibitor of activated protein C [ l , 21 which is a vitamin-K-dependent regulator of blood coagulation [3, 41. Formation of complexes between activated protein C and PCI is enhanced by sulfated polysaccharides such as heparin [5, 61. The 387-amino-acid structure of PCI is similar to that of a,-antichymotrypsin and a,-antitrypsin, and PCI is a member of the serpin (serine proteinase inhibitor) superfamily 17 -91. Serine-protease cleavage in the reactive center of serpin-family members results in the formation of covalent complexes and inactivation of the target enzyme. In PCI, the reactive center is cleaved C-terminal of Arg354, and may result in inactivation of activated protein

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Section: Antibodiesmentioning

confidence: 99%

Section: Ifma For Pci-psa Complexesmentioning

confidence: 99%

Complex formation between protein C inhibitor and prostate‐specific antigen in vitro and in human semen

Christensson

Lilja

1994

European Journal of Biochemistry

170

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“…Serum PSA occurs in several molecular forms, i.e. an unbound free form and complexed forms bound to a 1-antichymotrypsin (PSA-ACT), a 2-macroglobulin, protein C inhibitor, a 1-antitrypsin, and intera -trypsin inhibitor [3,4]. Recent reports show that measuring some molecular forms, including PSA complexed to a 1-protease inhibitor [5], complex PSA [6][7][8] and PSA-ACT [9,10], improve the discrimination of cancer from BPH in men with PSA levels of < 10.0 ng/mL.…”

Section: Introductionmentioning

confidence: 99%

Prostate‐specific antigen (PSA) complexed to α1‐antichymotrypsin improves prostate cancer detection using total PSA in Japanese patients with total PSA levels of 2.0–4.0 ng/mL

Kobayashi¹,

Nishizawa²,

Mitsumori³

et al. 2005

BJU International

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prostate volume-adjusted density were evaluated by receiver operating characteristic (ROC) analysis. RESULTSOf 1003 men enrolled, 547 met the biopsy criteria and a biopsy was taken in 315 (57.6%) patients. The area under the ROC curve for PSA-ACT (0.679) was significantly greater than that for total PSA (0.601, P = 0.04) and equivalent to that for the free-to-total ratio (0.686, P = 0.911) in 116 men, including 27 with cancer with total PSA levels of 2.0-4.0 ng/mL. PSA-ACT was more specific than the free-to-total ratio at a sensitivity of 95% (36% vs 18%, P < 0.05). The best variable for discriminating between cancer and benign disease in men with PSA levels of 2.0-4.0 ng/mL was PSA-ACT density (area under the curve 0.852) which provided 66% specificity at a sensitivity of 90%. CONCLUSIONSPSA-ACT is better than total PSA and equivalent to the free-to-total ratio for detecting prostate cancer in men with PSA levels of 2.0-4.0 ng/mL, and is thus useful for reducing the number of unnecessary biopsies.

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“…Human prostate-specific antigen (PSA) is a chymotrypsin-like serine protease that is secreted almost exclusively by prostatic tissue into the prostatic fluid. PSA is also released into the blood at low concentrations, whereupon it is bound to inhibitors and so is enzymatically inactive, though still immunoreactive [1]. In healthy males without clinical evidence of prostate cancer, the concentrations of PSA detected in the serum are very low (0-4 ng/ml).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the enzymatic activity of prostate‐specific antigen by boric acid and 3‐nitrophenyl boronic acid

et al. 2002

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Prostate-specific antigen in serum occurs predominantly in complex with alpha 1-antichymotrypsin

Cited by 855 publications

References 13 publications

Complex formation between protein C inhibitor and prostate‐specific antigen in vitro and in human semen

Complex formation between protein C inhibitor and prostate‐specific antigen in vitro and in human semen

Prostate‐specific antigen (PSA) complexed to α1‐antichymotrypsin improves prostate cancer detection using total PSA in Japanese patients with total PSA levels of 2.0–4.0 ng/mL

Inhibition of the enzymatic activity of prostate‐specific antigen by boric acid and 3‐nitrophenyl boronic acid

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