BACKGROUND: Galectin-3 is a multivalent carbohydrate-binding protein involved in cell adhesion, cell cycle control, immunomodulation, and cancer progression, including prostate cancer. Galectin-3 function is regulated by proteolytic cleavage that destroys galectin-3 multivalency while preserving carbohydrate-binding activity. In human semen, galectin-3 is present in seminal plasma and is also associated with prostasomes, exosome-like vesicles secreted by the prostate. In the current study, we characterized the proteolytic activity that cleaves galectin-3 in human seminal plasma. METHODS: An in vitro assay was developed to investigate galectin-3 cleavage in seminal plasma. The effect of protease inhibitors, divalent ion chelators, and Zn(2+) on the cleavage activity was determined. Proteases enriched from seminal plasma were tested for their ability to cleave galectin-3. Affinity purification and microsequence analysis were used to identify the cleavage site in galectin-3. RESULTS: Galectin-3 was identified in human seminal plasma in an intact and truncated form. Gelatinases enriched from seminal plasma did not cleave galectin-3. Inhibitor studies indicated that the galectin-3 cleavage activity in seminal plasma is a Zn(2+) sensitive, serine protease. Prostate specific antigen (PSA) was demonstrated to cleave galectin-3 between tyrosine¹⁰⁷-glycine¹⁰⁸ and produce a functionally active, monovalent lectin. CONCLUSIONS: PSA is a chymotrypsin-like serine protease secreted by the prostatic epithelium and normally functions in liquefaction of semen following ejaculation. Furthermore, PSA is implicated in the promotion of localized prostate tumors and bone metastases by its roles in immunomodulation, invasion, and apoptosis. Our results indicate that PSA regulates galectin-3 in human semen and may regulate galectin-3 function during prostate cancer progression.
BACKGROUND:Galectin-3 is a multivalent carbohydrate-binding protein involved in cell adhesion, cell cycle control, immunomodulation, and cancer progression, including prostate cancer. Galectin-3 function is regulated by proteolytic cleavage that destroys galectin-3 multivalency while preserving carbohydrate-binding activity. In human semen, galectin-3 is present in seminal plasma and is also associated with prostasomes, exosome-like vesicles secreted by the prostate. In the current study, we characterized the proteolytic activity that cleaves galectin-3 in human seminal plasma. METHODS: An in vitro assay was developed to investigate galectin-3 cleavage in seminal plasma. The effect of protease inhibitors, divalent ion chelators, and Zn(2+) on the cleavage activity was determined. Proteases enriched from seminal plasma were tested for their ability to cleave galectin-3. Affinity purification and microsequence analysis were used to identify the cleavage site in galectin-3. RESULTS:Galectin-3 was identified in human seminal plasma in an intact and truncated form. Gelatinases enriched from seminal plasma did not cleave galectin-3. Inhibitor studies indicated that the galectin-3 cleavage activity in seminal plasma is a Zn(2+) sensitive, serine protease. Prostate specific antigen (PSA) was demonstrated to cleave galectin-3 between tyrosine¹⁰⁷-glycine¹⁰⁸ and produce a functionally active, monovalent lectin. CONCLUSIONS:PSA is a chymotrypsin-like serine protease secreted by the prostatic epithelium and normally functions in liquefaction of semen following ejaculation. Furthermore, PSA is implicated in the promotion of localized prostate tumors and bone metastases by its roles in immunomodulation, invasion, and apoptosis. Our results indicate that PSA regulates galectin-3 in human semen and may regulate galectin-3 function during prostate cancer progression.
Authors: Vitaly Balan; Pratima Nangia-Makker; Ann G Schwartz; Young Suk Jung; Larry Tait; Victor Hogan; Tirza Raz; Yi Wang; Zeng Quan Yang; Gen Sheng Wu; Yongjun Guo; Huixiang Li; Judith Abrams; Fergus J Couch; Wilma L Lingle; Ricardo V Lloyd; Stephen P Ethier; Michael A Tainsky; Avraham Raz Journal: Cancer Res Date: 2008-12-15 Impact factor: 12.701
Authors: Jennifer L Jones; Sarika Saraswati; Ashley S Block; Cheryl F Lichti; Maha Mahadevan; Alan B Diekman Journal: Glycoconj J Date: 2009-10-15 Impact factor: 2.916
Authors: Yi Wang; Pratima Nangia-Makker; Larry Tait; Vitaly Balan; Victor Hogan; Kenneth J Pienta; Avraham Raz Journal: Am J Pathol Date: 2009-03-12 Impact factor: 4.307
Authors: Pratima Nangia-Makker; Tirza Raz; Larry Tait; Victor Hogan; Rafael Fridman; Avraham Raz Journal: Cancer Res Date: 2007-12-15 Impact factor: 12.701
Authors: Judith S Knapp; Soum D Lokeshwar; Ulrich Vogel; Jörg Hennenlotter; Christian Schwentner; Mario W Kramer; Arnulf Stenzl; Axel S Merseburger Journal: World J Urol Date: 2012-08-15 Impact factor: 4.226