CD169+ macrophages mediate pathological formation of woven bone in skeletal lesions of prostate cancer

Wu, Andy C., He, Yaowu, Broomfield, Amy, Paatan, Nicoll J., Harrington, Brittney S., Tseng, Hsu-Wen, Beaven, Elizabeth A., Kiernan, Deirdre M., Swindle, Peter, Clubb, Adrian B., Levesque, Jean-Pierre, Winkler, Ingrid G., Ling, Ming-Tat, Srinivasan, Bhuvana, Hooper, John D. and Pettit, Allison R. (2016) CD169+ macrophages mediate pathological formation of woven bone in skeletal lesions of prostate cancer. Journal of Pathology, 239 2: 218-230. doi:10.1002/path.4718

Author Wu, Andy C.
He, Yaowu
Broomfield, Amy
Paatan, Nicoll J.
Harrington, Brittney S.
Tseng, Hsu-Wen
Beaven, Elizabeth A.
Kiernan, Deirdre M.
Swindle, Peter
Clubb, Adrian B.
Levesque, Jean-Pierre
Winkler, Ingrid G.
Ling, Ming-Tat
Srinivasan, Bhuvana
Hooper, John D.
Pettit, Allison R.
Title CD169+ macrophages mediate pathological formation of woven bone in skeletal lesions of prostate cancer
Formatted title
CD169+ macrophages mediate pathological formation of woven bone in skeletal lesions of prostate cancer
Journal name Journal of Pathology   Check publisher's open access policy
ISSN 0022-3417
Publication date 2016
Year available 2016
Sub-type Article (original research)
DOI 10.1002/path.4718
Open Access Status Not Open Access
Volume 239
Issue 2
Start page 218
End page 230
Total pages 34
Place of publication Chichester, West Sussex, United Kingdom
Publisher John Wiley & Sons
Collection year 2017
Language eng
Formatted abstract
Skeletal metastases present a major clinical challenge for prostate cancer patient care, inflicting distinctive mixed osteoblastic and osteolytic lesions that cause morbidity and refractory skeletal complications. Macrophages are abundant in bone and bone marrow and can influence both osteoblast and osteoclast function in physiology and pathology. Herein we examined the role of macrophages in prostate cancer bone lesions, particularly the osteoblastic response. First, macrophage and lymphocyte distributions were qualitatively assessed in patient's prostate cancer skeletal lesions by immunohistochemistry. Second, macrophage functional contributions to prostate tumour growth in bone were explored using an immune-competent mouse model combined with two independent approaches to achieve in vivo macrophage depletion: liposome encapsulated clodronate that depletes phagocytic cells (including macrophages and osteoclasts); and targeted depletion of CD169+ macrophages using a suicide gene knock-in model. Immunohistochemistry and histomorphometric analysis were performed to quantitatively assess cancer-induced bone changes. In human bone metastasis specimens, CD68+ macrophages were consistently located within the tumour mass and at the tumour/bone marrow margins. Osteal macrophages (osteomacs) were associated with pathological woven bone within the metastatic lesions. In contrast, lymphocytes were inconsistently present in prostate cancer skeletal lesions and when detected had varied distributions. In the immune-competent mouse model, CD169+ macrophage ablation significantly inhibited prostate cancer-induced woven bone formation suggesting that CD169+ macrophages within pathological woven bone are integral to tumour-induced bone formation. In contrast pan-phagocytic, but not targeted CD169+ macrophage depletion resulted in increased tumour mass, indicating that CD169neg macrophage subset(s) and/or osteoclasts influenced tumour growth. In summary, these observations indicate a prominent role for macrophages in prostate cancer bone metastasis that may be therapeutically targetable to reduce the negative skeletal impacts of this malignancy, including tumour-induced bone modelling.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
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Created: Tue, 26 Apr 2016, 13:35:40 EST by Andy Wu on behalf of Mater Research Institute-UQ