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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/17276

Title: Kallikrein-related Peptidase Signalling via Proteinase-Activated Receptors
Authors: Oikonomopoulou, Aikaterini
Advisor: Diamandis, Eleftherios P.
Department: Laboratory Medicine and Pathobiology
Keywords: kallikrein-related peptidases
proteinase-activated receptors
cancer
inflammation
Issue Date: 26-Feb-2009
Abstract: The family of human kallikrein-related peptidases (KLKs) numbers 15 serine proteinases implicated in tumour progression. Despite the wide tissue distribution of KLKs and the numerous reports of their differential expression in pathological settings, the signalling mechanism(s) whereby these enzymes regulate tissue function are not yet known. Further, knowledge of the levels of their activity, as well as of their potential endogenous targets, has only been extracted from in vitro studies and cell culture systems. We hypothesized that KLKs can trigger tumour signalling via proteinase-activated receptors (PARs), a family of G-protein-coupled receptors. To test our hypothesis, we evaluated the ability of KLKs 5, 6, and 14: to activate or prevent signalling via PARs 1, 2, and 4 in cells and tissues expressing these receptors. Further, we used a novel activity-based probe approach, coupled with conventional immunoassay (ELISA), to determine the abundance of active KLK6 relative to total immunoreactive KLK6 in cancer-related biological fluids. We concluded that KLKs can regulate multiple signalling pathways triggered by PARs 1, 2, and 4, resulting in calcium release, platelet aggregation and vascular relaxation, and they can cause murine inflammation. Further, our activity-based ELISA demonstrated the presence of active KLK6 in ovarian cancer ascites fluids and cancer cell supernatants. We, therefore, suggest that tumours can produce active KLKs, which can potentially control tumour behaviour by regulating PAR activity.
URI: http://hdl.handle.net/1807/17276
Appears in Collections:Doctoral
Department of Laboratory Medicine and Pathobiology - Doctoral theses

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