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Functional proteomics of kallikrein-related peptidases in ovarian cancer ascites fluid
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Katerina Oikonomopoulou
Published/Copyright:
February 24, 2010
Abstract
Kallikrein-related peptidases (KLKs) are secreted serine proteinases with trypsin or chymotrypsin-like activity. Several family members, such as KLKs 6 and 10, are potential ovarian cancer biomarkers. Recently, using a newly developed assay for active KLK6, we found that only a very small proportion of immunoreactive KLK6 in tumor-derived clinical samples (malignant ascites fluid), in cerebrospinal fluid, and in cancer cell line supernatants is enzymatically active. We therefore hypothesized that a proportion of other immunoreactive KLKs in such samples could be present, but might be partly complexed to endogenous serine proteinase inhibitors. Using a combination of immunological isolation of the enzymes, activity-based probe analysis and proteomics, we identified active KLK10 in ovarian cancer ascites and we provide preliminary data that the activity of other KLKs present in these samples can be decreased by known proteinase inhibitors (e.g., α2-macroglobulin, α1-antitrypsin). Our data suggest that the enzymatic activity of ovarian cancer-released KLKs that are detected by regular immunoassays is low in vivo and very likely regulated by proteinase inhibitors.
Keywords: activity-based probe (ABP); ascites fluid; chymotrypsin-like activity; human kallikrein-related peptidase (KLK); serine proteinase; serine proteinase inhibitor; trypsin-like activity
Received: 2009-11-16
Accepted: 2010-1-18
Published Online: 2010-02-24
Published in Print: 2010-04-01
©2010 by Walter de Gruyter Berlin New York
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- The 3rd International Symposium on Kallikreins and Kallikrein-Related Peptidases
- HIGHLIGHT: 3RD INTERNATIONAL SYMPOSIUM ON KALLIKREINS AND KALLIKREIN-RELATED PEPTIDASES
- Kallikrein-related peptidases: proteolysis and signaling in cancer, the new frontier
- Functional intersection of the kallikrein-related peptidases (KLKs) and thrombostasis axis
- Kallikrein-related peptidases: bridges between immune functions and extracellular matrix degradation
- Prostate-specific antigen: an overlooked candidate for the targeted treatment and selective imaging of prostate cancer
- Tissue kallikrein in cardiovascular, cerebrovascular and renal diseases and skin wound healing
- Natural and engineered kallikrein inhibitors: an emerging pharmacopoeia
- Klk8, a multifunctional protease in the brain and skin: analysis of knockout mice
- Functional proteomics of kallikrein-related peptidases in ovarian cancer ascites fluid
- Polyclonal antibodies against kallikrein-related peptidase 4 (KLK4): immunohistochemical assessment of KLK4 expression in healthy tissues and prostate cancer
- Immunohistochemical analysis of kallikrein-related peptidases in the normal kidney and renal tumors: potential clinical implications
- Dysregulation of kallikrein-related peptidases in renal cell carcinoma: potential targets of miRNAs
- Analysis of an engineered plasma kallikrein inhibitor and its effect on contact activation
- Increased blood pressure and water intake in transgenic mice expressing rat tonin in the brain
- A structural network associated with the kallikrein-kinin and renin-angiotensin systems
- Analyzing the protease web in skin: meprin metalloproteases are activated specifically by KLK4, 5 and 8 vice versa leading to processing of proKLK7 thereby triggering its activation
- Expression of PSA-RP2, an alternatively spliced variant from the PSA gene, is increased in prostate cancer tissues but the protein is not secreted from prostate cancer cells
- KLK5 gene expression is severely upregulated in androgen-independent prostate cancer cells after treatment with the chemotherapeutic agents docetaxel and mitoxantrone
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Articles in the same Issue
- Guest Editorial
- The 3rd International Symposium on Kallikreins and Kallikrein-Related Peptidases
- HIGHLIGHT: 3RD INTERNATIONAL SYMPOSIUM ON KALLIKREINS AND KALLIKREIN-RELATED PEPTIDASES
- Kallikrein-related peptidases: proteolysis and signaling in cancer, the new frontier
- Functional intersection of the kallikrein-related peptidases (KLKs) and thrombostasis axis
- Kallikrein-related peptidases: bridges between immune functions and extracellular matrix degradation
- Prostate-specific antigen: an overlooked candidate for the targeted treatment and selective imaging of prostate cancer
- Tissue kallikrein in cardiovascular, cerebrovascular and renal diseases and skin wound healing
- Natural and engineered kallikrein inhibitors: an emerging pharmacopoeia
- Klk8, a multifunctional protease in the brain and skin: analysis of knockout mice
- Functional proteomics of kallikrein-related peptidases in ovarian cancer ascites fluid
- Polyclonal antibodies against kallikrein-related peptidase 4 (KLK4): immunohistochemical assessment of KLK4 expression in healthy tissues and prostate cancer
- Immunohistochemical analysis of kallikrein-related peptidases in the normal kidney and renal tumors: potential clinical implications
- Dysregulation of kallikrein-related peptidases in renal cell carcinoma: potential targets of miRNAs
- Analysis of an engineered plasma kallikrein inhibitor and its effect on contact activation
- Increased blood pressure and water intake in transgenic mice expressing rat tonin in the brain
- A structural network associated with the kallikrein-kinin and renin-angiotensin systems
- Analyzing the protease web in skin: meprin metalloproteases are activated specifically by KLK4, 5 and 8 vice versa leading to processing of proKLK7 thereby triggering its activation
- Expression of PSA-RP2, an alternatively spliced variant from the PSA gene, is increased in prostate cancer tissues but the protein is not secreted from prostate cancer cells
- KLK5 gene expression is severely upregulated in androgen-independent prostate cancer cells after treatment with the chemotherapeutic agents docetaxel and mitoxantrone
- Identification of IGFBP-3 fragments generated by KLK2 and prevention of fragmentation by KLK2-inhibiting peptides
