Complex formation between human prostate-specific antigen and protease inhibitors in mouse plasma
Autor: | Tero Riipi, Hannu Koistinen, Lei Zhu, Ulf-Håkan Stenman, Can Hekim, Pirjo Laakkonen |
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Rok vydání: | 2009 |
Předmět: |
medicine.medical_specialty
Urology medicine.medical_treatment Serpin urologic and male genital diseases 03 medical and health sciences 0302 clinical medicine Antigen Prostate Internal medicine LNCaP medicine 030304 developmental biology 0303 health sciences Protease medicine.diagnostic_test business.industry 3. Good health Transplantation Prostate-specific antigen medicine.anatomical_structure Endocrinology Oncology 030220 oncology & carcinogenesis Immunoassay Cancer research business |
Zdroj: | The Prostate. 70:482-490 |
ISSN: | 0270-4137 |
Popis: | BACKGROUND When secreted from the prostate, most of prostate-specific antigen (PSA) is free and enzymatically active. Upon reaching circulation, active PSA is inactivated by complex formation with protease inhibitors. To justify the use of mouse models for evaluation of the function of PSA and for studies on therapeutic modalities based on modulation of PSA activity, it is important to know whether PSA complexation is similar in mouse and man. METHODS To characterize the circulating forms of PSA in mouse, we used subcutaneous LNCaP and 22RV1 human prostate cancer cell xenograft tumor models. We also added PSA directly to mouse serum. Free and total PSA were measured by immunoassay, and PSA complexes were extracted by immunopurification followed by SDS–PAGE, in-gel trypsin digestion and identification of signature peptides by mass spectrometry. RESULTS In mice bearing xenograft tumors, 68% of the immunoreactive PSA occurred in complex, and when added to mouse serum, over 70% of PSA forms complexes that comprises α2-macroglobulin and members of the α1-antitrypsin (AAT) family. CONCLUSION In mouse plasma, PSA forms complexes similar to those in man, but the major immunoreactive complex contains AAT rather than α1-antichymotrypsin, which is the main complex forming serpin in man. The complex formation of PSA produced by xenograft tumor models in mice is similar to that of human prostate tumors with respect to the complexation of PSA. Prostate 70: 482–490, 2010. © 2009 Wiley-Liss, Inc. |
Databáze: | OpenAIRE |
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