Journal of Andrology, Vol 20, Issue 3 348-355, Copyright © 1999 by The American Society of Andrology

JOURNAL ARTICLE

Measurement of prostate-specific antigen and human glandular kallikrein 2 in different body fluids

J. Lovgren, C. Valtonen-Andre, K. Marsal, H. Lilja and A. Lundwall
Department of Laboratory Medicine, Lund University, University Hospital, Malmo, Sweden.

It has been demonstrated that prostate-specific antigen (PSA), in spite of its name, can be detected in body fluids and tumors from a variety of organs. Investigations have shown that human glandular kallikrein 2 (hK2), a related prostate-secreted protease, can activate the zymogen form of PSA, suggesting that the two enzymes might work as a functional unit, with hK2 as the activator molecule and PSA as the effector molecule. If this is true, then hK2 should be found together with PSA in body fluids other than seminal plasma, as well. Recently, a sensitive and specific assay was devised for hK2, enabling its measurement in picogram quantities. With this assay, the concentration of hK2 was determined in samples of seminal plasma, amniotic fluid, breast milk, and saliva. Simultaneously, the samples were assayed for molecular forms of PSA. In seminal plasma, the mean PSA concentration was 0.82 mg/ml, while the hK2 level was around two orders of magnitude lower: mean value, 6.4 microg/ml. Approximately the same ratio of PSA to hK2 as in seminal plasma was found in amniotic fluid and breast milk, but in most samples, the hK2 values were too low for direct measurements and had to be concentrated prior to analysis. Measurable levels of PSA, all in the free form, were detected in amniotic fluid at the thirteenth week of gestation and then gradually increased to levels around and over 1 microg/L from the twentieth week. Significant levels of PSA were detected in amniotic fluid collected at delivery, also. Measurable levels of mammary PSA were primarily detected in colostrum, with a range from less than 0.03 microg/L to 2.1 mg/L. Around half of the molecules were in complex with protease inhibitor. Most surprisingly, determinations on saliva samples showed that none of them had detectable PSA levels but had measurable concentrations of hK2 with a mean value, 0.09 microg/L. The presence in saliva suggests that hK2 can be the human equivalent to one of the mouse salivary kallikreins with important biological function, like the epidermal growth factor-binding protein or the gamma subunit of nerve growth factor. However, this was ruled out, as a phylogenetic analysis showed that the human and mouse glandular kallikreins evolved independently from a common precursor after the separation of the primate and rodent lineages. In conclusion, the measurements show that in addition to the previously known secretion in seminal plasma, hK2 is secreted in amniotic fluid, breast milk, and saliva. Furthermore, the concerted expression of PSA and hK2 in seminal plasma, amniotic fluid, and breast milk suggests that the two proteases might form a functional unit but not always as demonstrated by the sole presence of hK2 in saliva.

This article has been cited by other articles:

				M. H. Slagter, A. Scorilas, L. J.G. Gooren, W. de Ronde, A. Soosaipillai, E. J. Giltay, M. Paliouras, and E. P. Diamandis Effect of Testosterone Administration on Serum and Urine Kallikrein Concentrations in Female-to-Male Transsexuals Clin. Chem., August 1, 2006; 52(8): 1546 - 1551. [Abstract] [Full Text] [PDF]

				S. Nettikadan, K. Radke, J. Johnson, J. Xu, M. Lynch, C. Mosher, and E. Henderson Detection and Quantification of Protein Biomarkers from Fewer than 10 Cells Mol. Cell. Proteomics, May 1, 2006; 5(5): 895 - 901. [Abstract] [Full Text] [PDF]

				L.-Y. Luo, S. J.C. Shan, M. B. Elliott, A. Soosaipillai, and E. P. Diamandis Purification and Characterization of Human Kallikrein 11, a Candidate Prostate and Ovarian Cancer Biomarker, from Seminal Plasma Clin. Cancer Res., February 1, 2006; 12(3): 742 - 750. [Abstract] [Full Text] [PDF]

				M. M. Hobbs, M. J. Steiner, P. J. Feldblum, and N. Padian HOBBS ET AL. REPLY Am. J. Epidemiol., October 1, 2005; 162(7): 706 - 706. [Full Text] [PDF]

				B. Fingleton, R. Menon, K. J. Carter, P. D. Overstreet, D. L. Hachey, L. M. Matrisian, and J. O. McIntyre Proteinase Activity in Human and Murine Saliva as a Biomarker for Proteinase Inhibitor Efficacy Clin. Cancer Res., December 1, 2004; 10(23): 7865 - 7874. [Abstract] [Full Text] [PDF]

				S. Janssen, C. M. Jakobsen, D. M. Rosen, R. M. Ricklis, U. Reineke, S. B. Christensen, H. Lilja, and S. R. Denmeade Screening a combinatorial peptide library to develop a human glandular kallikrein 2-activated prodrug as targeted therapy for prostate cancer Mol. Cancer Ther., November 1, 2004; 3(11): 1439 - 1450. [Abstract] [Full Text] [PDF]

				V. Vaisanen, S. Eriksson, K. K. Ivaska, H. Lilja, M. Nurmi, and K. Pettersson Development of Sensitive Immunoassays for Free and Total Human Glandular Kallikrein 2 Clin. Chem., September 1, 2004; 50(9): 1607 - 1617. [Abstract] [Full Text] [PDF]

				S. P. Balk, Y.-J. Ko, and G. J. Bubley Biology of Prostate-Specific Antigen J. Clin. Oncol., January 15, 2003; 21(2): 383 - 391. [Abstract] [Full Text] [PDF]

				E. P. Diamandis and G. M. Yousef Human Tissue Kallikreins: A Family of New Cancer Biomarkers Clin. Chem., August 1, 2002; 48(8): 1198 - 1205. [Abstract] [Full Text] [PDF]

				A. Ylikoski, K. Pettersson, J. Nurmi, K. Irjala, M. Karp, H. Lilja, T. Lovgren, and M. Nurmi Simultaneous Quantification of Prostate-specific Antigen and Human Glandular Kallikrein 2 mRNA in Blood Samples from Patients with Prostate Cancer and Benign Disease Clin. Chem., August 1, 2002; 48(8): 1265 - 1271. [Abstract] [Full Text] [PDF]

				A. David, N. Mabjeesh, I. Azar, S. Biton, S. Engel, J. Bernstein, J. Romano, Y. Avidor, T. Waks, Z. Eshhar, et al. Unusual Alternative Splicing within the Human Kallikrein Genes KLK2 and KLK3 Gives Rise to Novel Prostate-specific Proteins J. Biol. Chem., May 10, 2002; 277(20): 18084 - 18090. [Abstract] [Full Text] [PDF]

				J. A. Finlay, J. R. Day, C. L. Evans, R. Carlson, K. Kuus-Reichel, L. S. Millar, S. D. Mikolajczyk, M. Goodmanson, G. G. Klee, and H. G. Rittenhouse Development of a Dual Monoclonal Antibody Immunoassay for Total Human Kallikrein 2 Clin. Chem., July 1, 2001; 47(7): 1218 - 1224. [Abstract] [Full Text] [PDF]

				G. M. Yousef and E. P. Diamandis The New Human Tissue Kallikrein Gene Family: Structure, Function, and Association to Disease Endocr. Rev., April 1, 2001; 22(2): 184 - 204. [Abstract] [Full Text]

				A. Paju, A. Bjartell, W.-M. Zhang, S. Nordling, A. Borgstrom, J. Hansson, and U.-H. Stenman Expression and Characterization of Trypsinogen Produced in the Human Male Genital Tract Am. J. Pathol., December 1, 2000; 157(6): 2011 - 2021. [Abstract] [Full Text] [PDF]

				C. Stephan, K. Jung, M. Lein, P. Sinha, D. Schnorr, and S. A. Loening Molecular Forms of Prostate-specific Antigen and Human Kallikrein 2 as Promising Tools for Early Diagnosis of Prostate Cancer Cancer Epidemiol. Biomarkers Prev., November 1, 2000; 9(11): 1133 - 1147. [Abstract] [Full Text]

				C. Becker, T. Piironen, J. Kiviniemi, H. Lilja, and K. Pettersson Sensitive and Specific Immunodetection of Human Glandular Kallikrein 2 in Serum Clin. Chem., February 1, 2000; 46(2): 198 - 206. [Abstract] [Full Text] [PDF]