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Macrophage cathepsin K promotes prostate tumor progression in bone

Oncogene volume 32, pages 1580–1593 (2013)Cite this article

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Abstract

Bone marrow macrophages (BMMs) share common progenitors with osteoclasts and are critical components of bone–tumor microenvironment; however, their function in prostate tumor growth in the skeleton has not been explored. BMMs are the major source of inflammatory factors and proteases, including cysteine protease cathepsin K (CTSK). In this study, utilizing mice deficient in CTSK, we demonstrate the critical involvement of this potent collagenase in tumor progression in bone. We present the evidence that tumor growth and progression in the bone are impaired in the absence of CTSK. Most importantly, we show for the first time that BMM-supplied CTSK may be involved in CCL2- and COX-2-driven pathways that contribute to tumor progression in bone. Together, our data unravel novel roles for CTSK in macrophage-regulated processes, and provide evidence for close interplay between inflammatory, osteolytic and tumor cell-driven events in the bone–tumor microenvironment.

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Acknowledgements

We gratefully acknowledge Dr Lisa Coussens (UCSF, CA) for providing breeding pairs of immuno-deficient (FVB/N/N5, Rag-1−/−, Cat K+/+(WT)) and (FVB/N/N5, Rag-1−/−, Cat K−/− (CTSK KO)) mice, as well as immuno-competent (FVB/N/N5 Cat K+/+ (WT)) and (FVB/N/N5 Cat K−/− (CTSK KO)) mice used in this study. We also thank Dr Bonnie Sloane for providing CTSB antibodies, Dr Kamiar Moin and the Microscopy, Imaging and Cytometry Resources Core for assistance with confocal and conventional light microscopy analyses, and Dr Karin list for critical review of this manuscript. Grant support was provided by DOD PC074031, DOD PC030325, Wayne State University start-up fund and MICR: P30 CA 22453.

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  1. Department of Pharmacology, Wayne State University School of Medicine, Detroit,

    M K Herroon, E Rajagurubandara, D L Rudy, A Chalasani, A L Hardaway & I Podgorski

  2. Karmanos Cancer Institute, Detroit, MI, USA

    I Podgorski

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  1. M K Herroon
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Herroon, M., Rajagurubandara, E., Rudy, D. et al. Macrophage cathepsin K promotes prostate tumor progression in bone. Oncogene 32, 1580–1593 (2013). https://doi.org/10.1038/onc.2012.166

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