Metastasis of ovarian cancer is mediated by kallikrein related peptidases

Dong, Ying, Loessner, Daniela, Irving-Rodgers, Helen, Obermair, Andreas, Nicklin, James L., & Clements, Judith A. (2014) Metastasis of ovarian cancer is mediated by kallikrein related peptidases. Clinical & Experimental Metastasis, 31(1), pp. 135-147.

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Abstract

Ovarian cancer, in particular epithelial ovarian cancer (EOC), is commonly diagnosed when the tumor has metastasized into the abdominal cavity with an accumulation of ascites fluid. Combining histopathology and genetic variations, EOC can be sub-grouped into Type-I and Type-II tumors, of which the latter are more aggressive and metastatic. Metastasis and chemoresistance are the key events associated with the tumor microenvironment that lead to a poor patient outcome. Kallikrein-related peptidases (KLKs) are aberrantly expressed in EOC, in particular, in the more metastatic Type-II tumors. KLKs are a family of 15 serine proteases that are expressed in diverse human tissues and involved in various patho-physiological processes. As extracellular enzymes, KLKs function in the hydrolysis of growth factors, proteases, cell membrane bound receptors, adhesion proteins, and cytokines initiating intracellular signaling pathways and their downstream events. High KLK levels are differentially associated with the prognosis of ovarian cancer patients, suggesting that they not only have application as biomarkers but also function in disease progression, and therefore are potential therapeutic targets. Recent studies have demonstrated the function of these proteases in promoting and/or suppressing the invasive behavior of ovarian cancer cells in metastasis in vitro and in vivo. Both conventional cell culture methods and three-dimensional platforms have been applied to mimic the ovarian cancer microenvironment of patients, such as the solid stromal matrix and ascites fluid. Here we summarize published studies to provide an overview of our understanding of the role of KLKs in EOC, and to lay the foundation for future research directions.

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ID Code: 66508
Item Type: Journal Article
Refereed: Yes
Keywords: Ascites microenvironment, Chemoresistance, Kallikrein-related peptidases, Metastasis, Multicellular aggregation, Serous ovarian cancer
DOI: 10.1007/s10585-013-9615-4
ISSN: 0262-0898
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Funding:
  • CANCER COUNCIL QLD/1034134
  • AISRF-BIOTECHNOLOGY/BF060023
Copyright Owner: Copyright 2013 The Author(s)
Copyright Statement: This article is published with open access at Springerlink.com
Deposited On: 22 Jan 2014 22:46
Last Modified: 17 Sep 2016 21:29

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