International Protease Network

Oncology Research Centre
University of New South Wales
Level 2, Clinical Sciences Building,Prince of Wales Hospital, Barker St., Randwick, NSW 2031
Email: p.russell@unsw.edu.au
Tel: +61-2- 9382 2610
Fax: +61-2-9382 2629
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Research

Our research centres on the complex role of proteases in the invasion and metastases of cancer, in particular in the bladder and prostate. Changes of protease expression may play an important role in cancer progression and can be used as diagnostic markers of potential aggression and as targets for drug treatment. Recent publications have shown that the extracellular matrix in tumor tissue is not only a barrier for invasion, but also a protector, keeping cancer cells isolated from cytotoxic drugs. Proteases that can break down matrix can increase the accessibility of molecular therapeutics in tumors. It is possible that different proteases play different roles in cancer progression, their expression may vary at different stages of tumour development, and many novel proteases are still yet to be discovered. We have used an assay developed by Dr Robert Whittaker (ex-CSIRO) to determine a profile of proteases that are broadly classified as serine, cysteine, metallo- and aspartic proteases expressed by prostate cancer cell lines of varying agressiveness. Our preliminary data have shown that protease activity against at least five amino acid specific substrates varies in six prostate cancer cell lines with different metastatic potentials. Dr Zhenzun Zhao in my group has successfully developed an in-gel protease activity assay which, together with 2D electrophoresis and mass spectrometry (MS), enables us to quickly and easily separate and identify proteases in biological samples. The successful identification of a protease, urokinase, in a prostate cancer cell line demonstrated the feasibility of this method. Identification and functional studies of these proteases should not only increase our understanding of cancer progression but may also provide molecular markers for diagnosis and targets for drug treatment.

Collaborations

Publications

Grant AJ, Russell PJ, Raghavan D. Elastase activity of human bladder cancer cell lines from highly invasive tumours. Biochim Biophys Res Comm 1989;162:308﷓15.

Grant AJ, Russell PJ, Raghavan D. Active and pro-plasminogen activator on the surface of human bladder cancer cells derived from a high grade invasive tumour. Biochem Biophys Res Comm 1990; 172:870-876.

Daja MM, Niu X, Zhao Z, Brown JM, Russell PJ. Characterization of expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in prostate cancer cell lines. Prostate Cancer and Prostatic Diseases, 2002;6:15-26.

Seetoo D-Q, Crowe PJ, Russell PJ, Yang J-L, Quantitative expression of protein markers of plasminogen activation system in prognosis of colorectal cancer. J Surg Oncol 2003; 82:184-193.

Zhao Z, Russell PJ. Trypsin activity assay in substrate-specific 1-D and 2-D gels: A powerful method to separate and characterise novel proteases in active form in biological samples. Electrophoresis 2003;24(18):3284-3288.

Zhao Z, Raftery MJ, Niu XM, Daja MM and Russell PJ. Characterization and identification of urokinase-type plasminogen activator (uPA) in secreted proteins from a prostate cancer cell line, PC-3. Electrophoresis, 2004, In press.

Li Y, Rizvi SMA, Brown JM, Cozzi PJ, Qu CF, Ow, KT, Tam PN, Perkins AC, Russell PJ, Allen BJ. Antigenic expression of human metastatic prostate cancer lines and primary prostate cancer for in vitro multiple alpha-targeted therapy with 213Bi- conjugates. In revision for International Journal of Radiation Oncology Biology Physics (IJROBP).