title: Bone marrow macrophages support prostate cancer growth in bone.
abstract: Resident macrophages in bone play important roles in bone remodeling, repair, and hematopoietic stem cell maintenance, yet their role in skeletal metastasis remains under investigated. The purpose of this study was to determine the role of macrophages in prostate cancer skeletal metastasis, using two in vivo mouse models of conditional macrophage depletion. RM-1 syngeneic tumor growth was analyzed in an inducible macrophage (CSF-1 receptor positive cells) ablation model (MAFIA mice). There was a significant reduction in tumor growth in the tibiae of macrophage-ablated mice, compared with control non-ablated mice. Similar results were observed when macrophage ablation was performed using liposome-encapsulated clodronate and human PC-3 prostate cancer cells where tumor-bearing long bones had increased numbers of tumor associated-macrophages. Although tumors were consistently smaller in macrophage-depleted mice, paradoxical results of macrophage depletion on bone were observed. Histomorphometric and micro-CT analyses demonstrated that clodronate-treated mice had increased bone volume, while MAFIA mice had reduced bone volume. These results suggest that the effect of macrophage depletion on tumor growth was independent of its effect on bone responses and that macrophages in bone may be more important to tumor growth than the bone itself. In conclusion, resident macrophages play a pivotal role in prostate cancer growth in bone.
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Fabiana N
authors.initials: FN
authors.lastname: Soki
authors.affiliation: Department of Internal Medicine, National Medical Center, Jung-gu, Seoul, Korea.
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Yeo Won
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Jacqueline D
authors.initials: JD
authors.lastname: Jones
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.|Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, Korea.
authors.forename: Serk In
authors.initials: SI
authors.lastname: Park
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Koh
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Payam
authors.initials: P
authors.lastname: Entezami
authors.affiliation: Center for Cancer Biostatistics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Daignault-Newton
authors.affiliation: The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Hernan
authors.initials: H
authors.lastname: Roca
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.|Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Laurie K
authors.initials: LK
authors.lastname: McCauley
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D001859:Bone Neoplasms / Q000276:immunology* / Q000556:secondary; D001861:Bone Regeneration; D063646:Carcinogenesis; D048708:Cell Growth Processes; D045744:Cell Line, Tumor; D004002:Clodronic Acid / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D004002:Clodronic Acid; D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: MAFIA mouse; clodronate liposome; macrophages; prostate cancer; skeletal metastasis