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CD169+ macrophages mediate pathological formation of woven bone in skeletal lesions of prostate cancer
The Journal of pathology, 2016-06, Vol.239 (2), p.218-230
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
2016
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
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
Titel
CD169+ macrophages mediate pathological formation of woven bone in skeletal lesions of prostate cancer
Ist Teil von
The Journal of pathology, 2016-06, Vol.239 (2), p.218-230
Ort / Verlag
Chichester, UK: John Wiley & Sons, Ltd
Erscheinungsjahr
2016
Quelle
Wiley-Blackwell Full Collection
Beschreibungen/Notizen
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. 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 cell, but not targeted CD169+ macrophage depletion resulted in increased tumour mass, indicating that CD169− 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. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Sprache
Englisch
Identifikatoren
ISSN: 0022-3417
eISSN: 1096-9896
DOI: 10.1002/path.4718
Titel-ID: cdi_proquest_miscellaneous_1789049325
Format
–
Schlagworte
Aged
,
Aged, 80 and over
,
Animals
,
Bone Neoplasms - immunology
,
Bone Neoplasms - pathology
,
Bone Neoplasms - secondary
,
Cell Line, Tumor
,
Disease Models, Animal
,
Humans
,
macrophage
,
Macrophages - immunology
,
Macrophages - pathology
,
Male
,
Mice
,
Mice, Inbred C57BL
,
Neoplasm Metastasis
,
Osteoblasts - immunology
,
Osteoblasts - pathology
,
Osteoclasts - immunology
,
Osteoclasts - pathology
,
Prostate - immunology
,
Prostate - pathology
,
prostate cancer
,
Prostatic Neoplasms - immunology
,
Prostatic Neoplasms - pathology
,
Sialic Acid Binding Ig-like Lectin 1 - immunology
,
Sialic Acid Binding Ig-like Lectin 1 - metabolism
,
woven bone
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