Prostate‐specific human kallikrein (hK2) as a novel marker for prostate cancer

Young, Charles Y.F.; Seay, Thomas M.; Hogen, K. L.; Charlesworth, M. Cristine; Roche, Patrick C.; Klee, George G.; Tindall, Donald J.

doi:10.1002/(sici)1097-0045(1996)7+<17::aid-pros2>3.3.co;2-d

Cited by 5 publications

(7 citation statements)

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“…This result is in accordance with the results obtained by Corey et al 10 and Kawakami et al 11 but not with the results of Young et al 12 The patients that gave positive result for hK2 mRNA were also positive for PSA mRNA. Only in patients with hormone refractory PC, we found one patient who expressed PSA mRNA in blood while no hK2 mRNA was detected.…”

Section: Discussionsupporting

confidence: 87%

“…The results of Young et al 12 showed hK2 and PSA mRNA expression in 83% and 17% of all of the patients studied, respectively. It was surprising that PSA mRNA was not detectable in the blood samples from the patients with organ-confined and with locally advanced PC.…”

Section: Discussionmentioning

confidence: 87%

“…Young et al 12 were the first to report the detection of hK2 mRNA together with that of PSA mRNA by two qualitative RT-PCR assays. 7,12 They detected hK2 mRNA in 1 of 1 PC patient with prostate-confined disease, 2 of 3 patients with locally advanced disease and 2 of 2 patients with distant metastatic disease. PSA mRNA was detected only in 1 of 2 patients with distant metastatic disease.…”

Section: Discussionmentioning

confidence: 99%

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Simultaneous Quantification of Human Glandular Kallikrein 2 and Prostate-Specific Antigen mRNAs in Peripheral Blood from Prostate Cancer Patients

Ylikoski

Karp

Pettersson

et al. 2001

The Journal of Molecular Diagnostics

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We present a multiplexed and internally calibrated quantitative reverse transcription-PCR (QRT-PCR) assay to detect human glandular kallikrein 2 (hK2) and prostate-specific antigen (PSA) transcripts in blood samples from healthy subjects and prostate cancer (PC) patients. The assay detected 50 copies of hK2 and PSA mRNA, and 1 PSA-and 10 hK2-expressing LNCaP cells in the presence of 2.5 ؋ 10 6 PSA-and hK2-negative cells. In PC patients, 20 of 25 and 19 of 25 gave detectable PSA and hK2 mRNAs, respectively. Number of hK2 mRNA copies was significantly higher than that of PSA mRNA copies in patients with biochemically progressive (P ‫؍‬ 0.02) PC, and with locally advanced and metastasized (P ‫؍‬ 0.004) PC. Patients with rapidly progressive and hormone refractory PC gave detectable hK2 mRNA only in 2 of 8 and PSA mRNA in 3 of 8 patients. Neither PSA nor hK2 mRNAs were detected in 16 healthy subjects. PSA and hK2 discriminated PC patients with biochemically progressive and advanced disease from the controls and from the aggressive distant metastatic disease. The assay provides a reliable quantification of the number of hK2 and PSA mRNA copies, allows to discriminate PC cases from healthy subjects, and offers a tool for further studies on molecular staging of PC.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Simultaneous Quantification of Human Glandular Kallikrein 2 and Prostate-Specific Antigen mRNAs in Peripheral Blood from Prostate Cancer Patients

Ylikoski

Karp

Pettersson

et al. 2001

The Journal of Molecular Diagnostics

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“…Its biological function remains unknown, but it has been suggested that it participates in the liquefaction of seminal coagulum (12). Interest has recently focused on this protein since it appears to be a novel marker of prostate cancer and/or benign prostate adenoma (13)(14)(15). hK2 has been obtained as a recombinant protease and used to prepare immunogens (11,16), but it has also been recently isolated as an active enzyme from seminal plasma (17).…”

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confidence: 99%

Serpin-derived Peptide Substrates for Investigating the Substrate Specificity of Human Tissue Kallikreins hK1 and hK2

Bourgeois

Brillard-Bourdet

Deperthes³

et al. 1997

Journal of Biological Chemistry

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The third human tissue kallikrein to be identified, hK2, could be an alternate or complementary marker to kallikrein hK3 (prostate-specific antigen) for prostate diseases. Most of the hK2 in seminal plasma forms an inactive complex with protein C inhibitor (PCI), a serpin secreted by seminal vesicles. As serpin inhibitors behave as suicide substrates that are cleaved early in the interaction with their target enzyme, and kallikreins have different sensitivities to serpin inhibitors, we prepared a series of substrates with intramolecularly quenched fluorescence based on the sequences of the serpin reactive loops. They were used to compare the substrate specificities of hK1 and hK2, which both have trypsin-like specificity, and thus differ from chymotrypsin-like hK3. The serpin-derived peptides behaved as kallikrein substrates whose sensitivities reflected the specificity of the parent inhibitory proteins. Substrates derived from PCI were the most sensitive for both hK1 and hK2 with specificity constants of about 10 7 M ؊1 . s ؊1 . Those derived from antithrombin III and ␣ 2 -antiplasmin were more specific for hK2 while a kallistatin-derived substrate was specifically cleaved by hK1. hK1 and hK2 substrates of greater specificity were obtained using chimeric peptides based on the sequence of serpin reactive loops.The main difference between specificities of hK1 and hK2 arise because hK2 can accommodate positively charged as well as small residues at P 2 and requires an arginyl residue at P 1 . Thus, unlike hK1, hK2 does not cleave kininogen-derived substrates overlapping the region of N-terminal insertion of bradykinin in human kininogens.The human kallikrein gene family contains three well-characterized members, hKLK1, hKLK2 and hKLK3 (1). These genes have been mapped to chromosome 19 (2) and are translated to give rise to proteinases hK1, hK2, and hK3 respectively (1). The only human tissue kallikrein with an undisputed function is hK1, which releases vasoactive kinins from kininogens, but these proteinases may have several other functions, including the processing of hormone and other peptide precursors (reviewed in Refs. 3 and 4). hK3 is produced mainly in the prostate and is known essentially as a marker of prostatic diseases (see Ref. 5 for a recent review). It participates in sperm liquefaction by cleaving fibronectin and semenogelins, the major components of the seminal vesicle coagulum after ejaculation (6, 7) and possibly in the processing of IGFBP-3 1 (8). hK2 is also predominantly synthesized in the prostate epithelium. Its mRNA concentration in the prostate gland is 4 -7 times lower than that of hK3 (9, 10), and it is present in seminal plasma as high M r inactive complexes with protein C inhibitor and as low M r inactive fragments (11). Its biological function remains unknown, but it has been suggested that it participates in the liquefaction of seminal coagulum (12). Interest has recently focused on this protein since it appears to be a novel marker of prostate cancer and/or benign prostate adenoma (...

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“…These receptors, which comprise a G protein coupled receptor sub-family consisting of PAR 1 -PAR 4 , are irreversibly activated by the action of Table 1 Summary of studies examining proteolytic substrate specificity and prostate expression of kallikrein-related peptidases. (Sueiras-Diaz et al, 1994;Chagas et al, 1995;(Geiger and Clausnitzer, 1981;Fink et al, 1985;Bourgeois et al, 1997;Chen et al, 2000;Borgono et al, 2007b) Shaw and 2 Tryptic Arg SF; N; B; P; C Up (Bourgeois et al, 1997;Mikolajczyk et al, 1998;(Deperthes et al, 1995;Young et al, 1996;Lovgren et al, 1999a;Cloutier et al, 2002) Darson et al, 1997, Darson et al, 1999Tremblay et al, 1997;Lovgren et al, 1999b;Magklara et al, 2000;Herrala et al, 2001;Veveris-Lowe et al, 2005; 3 Chymotryptic Leu, Tyr, Phe, Gln, His, Asn, Leu, Ser SF; N; B; P; C Down …”

Section: Introductionmentioning

confidence: 99%

Prostatic trypsin-like kallikrein-related peptidases (KLKs) and other prostate-expressed tryptic proteinases as regulators of signalling via proteinase-activated receptors (PARs)

Ramsay

Reid

Adams

et al. 2008

BCHM

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The prostate is a site of high expression of serine proteinases including members of the kallikrein-related peptidase (KLK) family, as well as other secreted and membrane-anchored serine proteinases. It has been known for some time that members of this enzyme family elicit cellular responses by acting directly on cells. More recently, it has been recognised that for serine proteinases with specificity for cleavage after arginine and lysine residues (trypsin-like or tryptic enzymes) these cellular responses are often mediated by cleavage of members of the proteinase-activated receptor (PAR) family -a four member sub-family of G protein-coupled receptors. Here, we review the expression of PARs in prostate, the ability of prostatic trypsin-like KLKs and other prostateexpressed tryptic enzymes to cleave PARs, as well as the prostate cancer-associated consequences of PAR activation. In addition, we explore the dysregulation of trypsin-like serine proteinase activity through the loss of normal inhibitory mechanisms and potential interactions between these dysregulated enzymes leading to aberrant PAR activation, intracellular signalling and cancer-promoting cellular changes.

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Prostate‐specific human kallikrein (hK2) as a novel marker for prostate cancer

Cited by 5 publications

References 0 publications

Simultaneous Quantification of Human Glandular Kallikrein 2 and Prostate-Specific Antigen mRNAs in Peripheral Blood from Prostate Cancer Patients

Simultaneous Quantification of Human Glandular Kallikrein 2 and Prostate-Specific Antigen mRNAs in Peripheral Blood from Prostate Cancer Patients

Serpin-derived Peptide Substrates for Investigating the Substrate Specificity of Human Tissue Kallikreins hK1 and hK2

Prostatic trypsin-like kallikrein-related peptidases (KLKs) and other prostate-expressed tryptic proteinases as regulators of signalling via proteinase-activated receptors (PARs)

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