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

• DOI: 10.1002/path.4718
• Publication Date: 2016-03-22T13:05:58Z
• Authors: Andy C Wu; Yaowu He; Amy Broomfield; Nicoll J Paatan; Brittney S Harrin...; Hsu‐Wen Tseng; Elizabeth A Beaven; Deirdre M Kiernan; Peter Swindle; Adrian B Clubb; Jean‐Pierre Levesque; Ingrid G Winkler; Ming‐Tat Ling; Bhuvana Srinivasan; John D Hooper; Allison R Pettit
• Keywords: CD68; Osteolysis; Osteoimmunology

Skeletal metastases present a major clinical challenge for prostate cancer patient care, inflicting distinctive mixed osteoblastic and osteolytic lesions that cause morbidity refractory skeletal complications. Macrophages are abundant in bone marrow can influence both osteoblast osteoclast function physiology pathology. Herein, we examined the role of macrophages lesions, particularly response. First, macrophage lymphocyte distributions were qualitatively assessed patient's by immunohistochemistry. Second, functional contributions to tumour growth explored using an immune-competent mouse model combined with two independent approaches achieve vivo depletion: liposome encapsulated clodronate depletes phagocytic cells (including osteoclasts); targeted depletion CD169(+) suicide gene knock-in model. Immunohistochemistry histomorphometric analysis performed quantitatively assess cancer-induced changes. In human metastasis specimens, CD68(+) consistently located within mass. Osteal (osteomacs) associated pathological woven metastatic lesions. contrast, lymphocytes inconsistently when detected, had varied distributions. model, ablation significantly inhibited formation, suggesting integral tumour-induced formation. pan-phagocytic cell, but not resulted increased mass, indicating CD169(-) subset(s) and/or osteoclasts influenced growth. summary, these observations indicate prominent may be therapeutically targetable reduce negative impacts this malignancy, including modelling. Copyright © 2016 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.