Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/120956
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Type: | Journal article |
Title: | Clodronate-liposome mediated macrophage depletion abrogates multiple myeloma tumor establishment in vivo |
Author: | Opperman, K.S. Vandyke, K. Clark, K.C. Coulter, E.A. Hewett, D.R. Mrozik, K.M. Schwarz, N. Evdokiou, A. Croucher, P.I. Psaltis, P.J. Noll, J.E. Zannettino, A.C. |
Citation: | Neoplasia, 2019; 21(8):777-787 |
Publisher: | Ediciones Doyma S.A. |
Issue Date: | 2019 |
ISSN: | 0212-9787 1476-5586 |
Statement of Responsibility: | Khatora S. Opperman, Kate Vandyke, Kimberley C. Clark, Elizabeth A. Coulter, Duncan R. Hewett, Krzysztof M. Mrozik, Nisha Schwarz, Andreas Evdokiou, Peter I Croucher, Peter J Psaltis, Jacqueline E Noll and Andrew CW Zannettino |
Abstract: | Multiple myeloma is a fatal plasma cell malignancy that is reliant on the bone marrow microenvironment. The bone marrow is comprised of numerous cells of mesenchymal and hemopoietic origin. Of these, macrophages have been implicated to play a role in myeloma disease progression, angiogenesis, and drug resistance; however, the role of macrophages in myeloma disease establishment remains unknown. In this study, the antimyeloma efficacy of clodronate-liposome treatment, which globally and transiently depletes macrophages, was evaluated in the well-established C57BL/KaLwRijHsd murine model of myeloma. Our studies show, for the first time, that clodronate-liposome pretreatment abrogates myeloma tumor development in vivo. Clodronate-liposome administration resulted in depletion of CD169+ bone marrow-resident macrophages. Flow cytometric analysis revealed that clodronate-liposome pretreatment impaired myeloma plasma cell homing and retention within the bone marrow 24 hours postmyeloma plasma cell inoculation. This was attributed in part to decreased levels of macrophage-derived insulin-like growth factor 1. Moreover, a single dose of clodronate-liposome led to a significant reduction in myeloma tumor burden in KaLwRij mice with established disease. Collectively, these findings support a role for CD169-expressing bone marrow-resident macrophages in myeloma disease establishment and progression and demonstrate the potential of targeting macrophages as a therapy for myeloma patients. |
Keywords: | Cell Line, Tumor Macrophages Osteoblasts Animals Mice Multiple Myeloma Disease Models, Animal Disease Susceptibility Clodronic Acid Liposomes Cell Count Immunophenotyping Cell Movement Bone Density Conservation Agents Tumor Microenvironment Biomarkers |
Rights: | © 2019 The Authors. Published by Elsevier Inc. on behalf of Neoplasia Press, Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). |
DOI: | 10.1016/j.neo.2019.05.006 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1140996 |
Published version: | http://dx.doi.org/10.1016/j.neo.2019.05.006 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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hdl_120956.pdf | Published version | 695.58 kB | Adobe PDF | View/Open |
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