Cathepsin S from both tumour and tumour-associated cells promote cancer growth and neovascularisation

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    Recent murine studies have demonstrated that tumour-associated macrophages in the tumour microenvironment are a key source of the pro-tumourigenic cysteine protease, cathepsin S. We now show in a syngeneic colorectal carcinoma murine model that both tumour and tumour-associated cells contribute cathepsin S to promote neovascularisation and tumour growth. Cathepsin S depleted and control colorectal MC38 tumour cell lines were propagated in both wild type C57Bl/6 and cathepsin S null mice to provide stratified depletion of the protease from either the tumour, tumour-associated host cells, or both. Parallel analysis of these conditions showed that deletion of cathepsin S inhibited tumour growth and development, and revealed a clear contribution of both tumour and tumour-associated cell derived cathepsin S. The most significant impact on tumour development was obtained when the protease was depleted from both sources. Further characterisation revealed that the loss of cathepsin S led to impaired tumour vascularisation, which was complemented by a reduction in proliferation and increased apoptosis, consistent with reduced tumour growth. Analysis of cell types showed that in addition to the tumour cells, tumour-associated macrophages and endothelial cells can produce cathepsin S within the microenvironment. Taken together, these findings clearly highlight a manner by which tumour-associated cells can positively contribute to developing tumours and highlight cathepsin S as a therapeutic target in cancer.

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    • Cathepsin S from both tumor and tumor-associated cells

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    DOI

    Original languageEnglish
    Number of pages11
    Pages (from-to)2102-2112
    JournalInternational Journal of Cancer
    Journal publication dateNov 2013
    Issue number9
    Volume133
    Early online date29 May 2013
    DOIs
    Publication statusPublished - Nov 2013

      Research areas

    • proteases, cathepsin S, angiogenesis, tumorigenesis, stroma

    ID: 3466683