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.
Oncotarget. 2015 Oct 08 [Epub ahead of print]
Fabiana N Soki, Sun Wook Cho, Yeo Won Kim, Jacqueline D Jones, Serk In Park, Amy J Koh, Payam Entezami, Stephanie Daignault-Newton, Kenneth J Pienta, Hernan Roca, Laurie K McCauley
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA. , Department of Internal Medicine, National Medical Center, Jung-gu, Seoul, Korea. , Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA. , Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA. , Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. , Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA. , Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA. , Center for Cancer Biostatistics, University of Michigan, Ann Arbor, MI, USA. , The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. , Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA. , Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.