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Complex formation between human prostate‐specific antigen and protease inhibitors in mouse plasma
Author(s) -
Hekim Can,
Riipi Tero,
Zhu Lei,
Laakkonen Pirjo,
Stenman UlfHåkan,
Koistinen Hannu
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21082
Subject(s) - lncap , prostate cancer , prostate , prostate specific antigen , serpin , chemistry , antigen , cancer research , trypsin , endocrinology , cancer , medicine , immunology , biochemistry , enzyme , gene
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 α 2 ‐macroglobulin and members of the α 1 ‐antitrypsin (AAT) family. CONCLUSION In mouse plasma, PSA forms complexes similar to those in man, but the major immunoreactive complex contains AAT rather than α 1 ‐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.