{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:46:18Z","timestamp":1790876778386,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2001,5,31]],"date-time":"2001-05-31T00:00:00Z","timestamp":991267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2001,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Prostate\u2010specific antigen (PSA) targeted prodrugs are under development in our laboratory. Concentrations of total PSA and enzymatically active PSA produced by various human prostate cancer xenograft models have not been well characterized.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The concentration of PSA secreted into the extracellular fluid (ECF) in normal human prostate tissue, primary prostate cancers obtained directly from patients, and serially passageable human prostate cancer xenografts (PC\u201082, LNCaP, LAPC\u20104) were determined using Tandem assays. Percent enzymatically active PSA in the ECF and in conditioned media was also determined using a previously validated assay employing a monoclonal antibody to the PSA catalytic site. In addition, the concentration and activity of PSA within sera from men with and without prostate cancer, as well as from tumor\u2010bearing animals, was likewise assayed.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Normal human prostate tissue and primary human prostate cancers have high concentrations of PSA in the ECF (i.e., 1600\u20132100 nM). The majority of this PSA is enzymatically active (i.e., 80\u201390%). Human PC\u201082 prostate cancer xenografts also have high concentrations of PSA in the ECF (624\u2009\u00b1\u2009360 nM), and the majority of this PSA is also enzymatically active (i.e., 66\u2009\u00b1\u20094%). In contrast, much lower concentrations of PSA are found in the ECF from LNCaP (45\u2009\u00b1\u20099 nM) and LAPC\u20104 (7.3\u2009\u00b1\u20090.6 nM). Only a small portion of the total PSA isolated from DHT\u2010containing, serum\u2010free, conditioned media from these cell lines is enzymatically active (i.e., \u223c18%). While PSA was detected in all serum samples regardless of the type of host, no enzymatically active PSA was detected in any of these serum samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Prostate cancers obtained directly from patients produce and secrete large amounts of PSA, the majority of which is highly enzymatically active. In contrast, while PSA was detected in the sera, none of this PSA was enzymatically active. This is also the case for the human PC\u201082 prostate cancer xenografts. In contrast, LNCaP and LAPC\u20104 human prostate cancer xenograft models secrete \u223c70\u2013300\u2010fold less PSA in the ECF than prostate cancers from patients and the majority of this PSA is enzymatically inactive. Also, the serum from these animals had detectable PSA, but none of this PSA was enzymatically active. Thus, these latter two prostate cancer models define the least and the PC\u201082, the most, optimized xenograft model for screening PSA targeted prodrugs. Prostate 48:1\u20136, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.1075","type":"journal-article","created":{"date-parts":[[2004,10,28]],"date-time":"2004-10-28T09:06:58Z","timestamp":1098954418000},"page":"1-6","source":"Crossref","is-referenced-by-count":82,"title":["Concentration of enzymatically active prostate\u2010specific antigen (PSA) in the extracellular fluid of primary human prostate cancers and human prostate cancer xenograft models"],"prefix":"10.1002","volume":"48","author":[{"given":"Samuel R.","family":"Denmeade","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori J.","family":"Sokoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel W.","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed 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produce both N\u2010terminally mature and truncated prostate\u2010specific antigen isoforms","volume":"98","author":"Herrala A","year":"1998","journal-title":"Eur J Biochem"},{"key":"e_1_2_1_18_2","first-page":"1","article-title":"Characterization and processing of prostate\u2010specific antigen (hK3) and human glandular kallikrein 2 (hK2) secreted by LNCaP cells","volume":"2","author":"Veisenen V","year":"1999","journal-title":"Prostate Cancer Prostatic Dis"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0045(20000801)44:3<248::AID-PROS10>3.0.CO;2-D"},{"key":"e_1_2_1_20_2","first-page":"638","volume-title":"Comprehensive textbook of genitourinary oncology","author":"Lilja H","year":"2000"},{"key":"e_1_2_1_21_2","first-page":"3111","article-title":"Expression of pro form of prostate\u2010specific antigen by mammalian cells and its conversion to mature, active form by human kallikrein 2","volume":"50","author":"Kumar A","year":"1997","journal-title":"Cancer 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