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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
Statement of
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://
RMID: 0030119370
DOI: 10.1016/j.neo.2019.05.006
Grant ID:
Appears in Collections:Medicine publications

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