Complex formation between human prostate-specific antigen and protease inhibitors in mouse plasma

Area of Science:

• Biochemistry
• Oncology
• Proteomics

Background:

• Prostate-specific antigen (PSA) is secreted as active and forms complexes with protease inhibitors in circulation.
• Understanding PSA complexation in mice is crucial for validating mouse models in prostate cancer research.
• Investigating therapeutic strategies targeting PSA activity necessitates knowledge of its behavior in vivo.

Purpose of the Study:

• To characterize the circulating forms of PSA in mouse models.
• To compare PSA complexation in mice with that observed in humans.
• To validate the use of mouse xenograft models for studying PSA function and therapeutic interventions.

Main Methods:

• Utilized LNCaP and 22RV1 human prostate cancer xenograft models in mice.
• Administered PSA directly to mouse serum for in vitro analysis.
• Quantified free and total PSA via immunoassay and identified PSA complexes using mass spectrometry after immunopurification and SDS-PAGE.

Main Results:

• In mice with xenograft tumors, 68% of immunoreactive PSA was found in complexed form.
• Over 70% of PSA formed complexes when added to mouse serum.
• Identified PSA complexes primarily with alpha(2)-macroglobulin and alpha-1-antitrypsin (AAT) family members.

Conclusions:

• PSA forms complexes in mouse plasma that are similar to human complexation patterns.
• The primary serpin forming complexes with PSA in mice is AAT, differing from human alpha-1-antichymotrypsin.
• PSA complexation in mouse xenograft models mirrors that of human prostate tumors, supporting their use in research.