Bone marrow macrophages support prostate cancer growth in bone

Fabiana N. Soki, Sun Wook Cho, Yeo Won Kim, Jacqueline D. Jones, Serkin Park, Amy J. Koh, Payam Entezami, Stephanie Daignault-Newton, Kenneth J. Pienta, Hernan Roca, Laurie K. McCauley

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19 Citations (Scopus)

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 macrophageablated 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.

Original languageEnglish
Pages (from-to)35782-35796
Number of pages15
JournalOncotarget
Volume6
Issue number34
DOIs
Publication statusPublished - 2015 Jan 1

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Keywords

  • Clodronate liposome
  • Efferocytosis
  • Macrophages
  • MAFIA mouse
  • Prostate cancer
  • Skeletal metastasis

ASJC Scopus subject areas

  • Oncology

Cite this

Soki, F. N., Cho, S. W., Kim, Y. W., Jones, J. D., Park, S., Koh, A. J., Entezami, P., Daignault-Newton, S., Pienta, K. J., Roca, H., & McCauley, L. K. (2015). Bone marrow macrophages support prostate cancer growth in bone. Oncotarget, 6(34), 35782-35796. https://doi.org/10.18632/oncotarget.6042