University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Medical Biology
  • Medical Biology - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Medical Biology
  • Medical Biology - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    Cysteine cathepsin activity suppresses osteoclastogenesis of myeloid-derived suppressor cells in breast cancer

    Thumbnail
    Download
    Published version (9.832Mb)

    Citations
    Scopus
    Web of Science
    Altmetric
    20
    19
    Author
    Edgington-Mitchell, LE; Rautela, J; Duivenvoorden, HM; Jayatilleke, KM; van der Linden, WA; Verdoes, M; Bogyo, M; Parker, BS
    Date
    2015-09-29
    Source Title
    Oncotarget
    Publisher
    IMPACT JOURNALS LLC
    University of Melbourne Author/s
    Edgington-Mitchell, Laura; Rautela, Jai
    Affiliation
    Medical Biology (W.E.H.I.)
    Biochemistry and Molecular Biology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Edgington-Mitchell, L. E., Rautela, J., Duivenvoorden, H. M., Jayatilleke, K. M., van der Linden, W. A., Verdoes, M., Bogyo, M. & Parker, B. S. (2015). Cysteine cathepsin activity suppresses osteoclastogenesis of myeloid-derived suppressor cells in breast cancer. ONCOTARGET, 6 (29), pp.27008-27022. https://doi.org/10.18632/oncotarget.4714.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255597
    DOI
    10.18632/oncotarget.4714
    Abstract
    Cysteine cathepsin proteases contribute to many normal cellular functions, and their aberrant activity within various cell types can contribute to many diseases, including breast cancer. It is now well accepted that cathepsin proteases have numerous cell-specific functions within the tumor microenvironment that function to promote tumor growth and invasion, such that they may be valid targets for anti-metastatic therapeutic approaches. Using activity-based probes, we have examined the activity and expression of cysteine cathepsins in a mouse model of breast cancer metastasis to bone. In mice bearing highly metastatic tumors, we detected abundant cysteine cathepsin expression and activity in myeloid-derived suppressor cells (MDSCs). These immature immune cells have known metastasis-promoting roles, including immunosuppression and osteoclastogenesis, and we assessed the contribution of cysteine cathepsins to these functions. Blocking cysteine cathepsin activity with multiple small-molecule inhibitors resulted in enhanced differentiation of multinucleated osteoclasts. This highlights a potential role for cysteine cathepsin activity in suppressing the fusion of osteoclast precursor cells. In support of this hypothesis, we found that expression and activity of key cysteine cathepsins were downregulated during MDSC-osteoclast differentiation. Another cysteine protease, legumain, also inhibits osteoclastogenesis, in part through modulation of cathepsin L activity. Together, these data suggest that cysteine protease inhibition is associated with enhanced osteoclastogenesis, a process that has been implicated in bone metastasis.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45689]
    • Biochemistry and Molecular Biology - Research Publications [787]
    • Medical Biology - Research Publications [865]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors