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Development of peptides specifically modulating the activity of KLK2 and KLK3
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Hannu Koistinen
Published/Copyright:
May 15, 2008
Abstract
The prostate produces several proteases, the most abundant ones being kallikrein-related peptidase 3 (KLK3, PSA) and KLK2 (hK2), which are potential targets for tumor imaging and treatment. KLK3 expression is lower in malignant than in normal prostatic epithelium and it is further reduced in poorly differentiated tumors, in which the expression of KLK2 is increased. KLK3 has been shown to inhibit angiogenesis, whereas KLK2 may mediate tumor growth and invasion by participating in proteolytic cascades. Thus, it may be possible to control prostate cancer growth by modulating the proteolytic activity of KLK3 and KLK2. We have developed peptides that very specifically stimulate the activity of KLK3 or inhibit that of KLK2. Using these peptides we have established peptide-based methods for the determination of enzymatically active KLK3. The first-generation peptides are unstable in vivo and are rapidly cleared from the circulation. Currently we are modifying the peptides to make them suitable for in vivo applications. We have been able to considerably improve the stability of KLK2-binding peptides by cyclization. In this review we summarize the possible roles of KLK3 and KLK2 in prostate cancer and then concentrate on the development of peptides that modulate the activity of these proteases.
Published Online: 2008-05-15
Published in Print: 2008-06-01
©2008 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Editorial
- Kallikreins and kallikrein-related peptidases
- Guest Editorial
- The 2nd International Symposium on Kallikreins and Kallikrein-Related Peptidases (ISK 2007) and the Commemorative Gold Medal of the E.K. Frey–E. Werle Foundation of the Henning L. Voigt Family
- Highlight: Kallikrein, kinins and kallikrein-related peptidases
- Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7
- Development of peptides specifically modulating the activity of KLK2 and KLK3
- Kallikreins and proteinase-mediated signaling: proteinase-activated receptors (PARs) and the pathophysiology of inflammatory diseases and cancer
- Prostatic trypsin-like kallikrein-related peptidases (KLKs) and other prostate-expressed tryptic proteinases as regulators of signalling via proteinase-activated receptors (PARs)
- Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier functions
- A potential role for tissue kallikrein-related peptidases in human cervico-vaginal physiology
- microRNAs: a new frontier in kallikrein research
- Functions of KLK4 and MMP-20 in dental enamel formation
- Genetic deficiency in tissue kallikrein activity in mouse and man: effect on arteries, heart and kidney
- Development of diabetic cardiomyopathy and the kallikrein-kinin system – new insights from B1 and B2 receptor signaling
- Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by gene deletion of the kinin B1 receptor
- Attenuation of left ventricular dysfunction by an ACE inhibitor after myocardial infarction in a kininogen-deficient rat model
- Tissue kallikrein and kinin infusion promotes neovascularization in limb ischemia
- Kallikreins as microRNA targets: an in silico and experimental-based analysis
- Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration
- Immunofluorometric activity-based probe analysis of active KLK6 in biological fluids
- Kallikrein 6 is a mediator of K-RAS-dependent migration of colon carcinoma cells
- Gene expression changes associated with the anti-angiogenic activity of kallikrein-related peptidase 3 (KLK3) on human umbilical vein endothelial cells
- An AKT activity threshold regulates androgen-dependent and androgen-independent PSA expression in prostate cancer cell lines
- Quantitative RT-PCR analysis and immunohistochemical localization of the kallikrein-related peptidases 13 and 14 in lung
Keywords for this article
hK2;
kallikrein;
peptide modification;
phage display;
prostate cancer;
PSA
Articles in the same Issue
- Editorial
- Kallikreins and kallikrein-related peptidases
- Guest Editorial
- The 2nd International Symposium on Kallikreins and Kallikrein-Related Peptidases (ISK 2007) and the Commemorative Gold Medal of the E.K. Frey–E. Werle Foundation of the Henning L. Voigt Family
- Highlight: Kallikrein, kinins and kallikrein-related peptidases
- Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7
- Development of peptides specifically modulating the activity of KLK2 and KLK3
- Kallikreins and proteinase-mediated signaling: proteinase-activated receptors (PARs) and the pathophysiology of inflammatory diseases and cancer
- Prostatic trypsin-like kallikrein-related peptidases (KLKs) and other prostate-expressed tryptic proteinases as regulators of signalling via proteinase-activated receptors (PARs)
- Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier functions
- A potential role for tissue kallikrein-related peptidases in human cervico-vaginal physiology
- microRNAs: a new frontier in kallikrein research
- Functions of KLK4 and MMP-20 in dental enamel formation
- Genetic deficiency in tissue kallikrein activity in mouse and man: effect on arteries, heart and kidney
- Development of diabetic cardiomyopathy and the kallikrein-kinin system – new insights from B1 and B2 receptor signaling
- Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by gene deletion of the kinin B1 receptor
- Attenuation of left ventricular dysfunction by an ACE inhibitor after myocardial infarction in a kininogen-deficient rat model
- Tissue kallikrein and kinin infusion promotes neovascularization in limb ischemia
- Kallikreins as microRNA targets: an in silico and experimental-based analysis
- Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration
- Immunofluorometric activity-based probe analysis of active KLK6 in biological fluids
- Kallikrein 6 is a mediator of K-RAS-dependent migration of colon carcinoma cells
- Gene expression changes associated with the anti-angiogenic activity of kallikrein-related peptidase 3 (KLK3) on human umbilical vein endothelial cells
- An AKT activity threshold regulates androgen-dependent and androgen-independent PSA expression in prostate cancer cell lines
- Quantitative RT-PCR analysis and immunohistochemical localization of the kallikrein-related peptidases 13 and 14 in lung
