Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche

Lawson, Michelle A., McDonald, Michelle M., Kovacic, Natasa, Khoo, Weng Hua, Terry, Rachael L., Down, Jenny, Kaplan, Warren, Paton-Hough, Julia, Fellows, Clair, Pettitt, Jessica A., Dear, T.Neil, Van Valckenborgh, Els, Baldock, Paul A., Rogers, Michael J., Eaton, Colby L., Vanderkerken, Karin, Pettit, Allison R., Quinn, Julian M.W., Zannettino, Andrew C.W., Phan, Tri Giang and Croucher, Peter I. (2015) Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche. Nature Communications, 6 8983: . doi:10.1038/ncomms9983

Author Lawson, Michelle A.
McDonald, Michelle M.
Kovacic, Natasa
Khoo, Weng Hua
Terry, Rachael L.
Down, Jenny
Kaplan, Warren
Paton-Hough, Julia
Fellows, Clair
Pettitt, Jessica A.
Dear, T.Neil
Van Valckenborgh, Els
Baldock, Paul A.
Rogers, Michael J.
Eaton, Colby L.
Vanderkerken, Karin
Pettit, Allison R.
Quinn, Julian M.W.
Zannettino, Andrew C.W.
Phan, Tri Giang
Croucher, Peter I.
Title Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2015-12-03
Year available 2015
Sub-type Article (original research)
DOI 10.1038/ncomms9983
Open Access Status DOI
Volume 6
Issue 8983
Total pages 15
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1600 Chemistry
1300 Biochemistry, Genetics and Molecular Biology
3100 Physics and Astronomy
Abstract Multiple myeloma is largely incurable, despite development of therapies that target myeloma cell-intrinsic pathways. Disease relapse is thought to originate from dormant myeloma cells, localized in specialized niches, which resist therapy and repopulate the tumour. However, little is known about the niche, and how it exerts cell-extrinsic control over myeloma cell dormancy and reactivation. In this study, we track individual myeloma cells by intravital imaging as they colonize the endosteal niche, enter a dormant state and subsequently become activated to form colonies. We demonstrate that dormancy is a reversible state that is switched ‘on’ by engagement with bone-lining cells or osteoblasts, and switched ‘off’ by osteoclasts remodelling the endosteal niche. Dormant myeloma cells are resistant to chemotherapy that targets dividing cells. The demonstration that the endosteal niche is pivotal in controlling myeloma cell dormancy highlights the potential for targeting cell-extrinsic mechanisms to overcome cell-intrinsic drug resistance and prevent disease relapse.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID GNT1057706
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Official 2016 Collection
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Citation counts: TR Web of Science Citation Count  Cited 40 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 42 times in Scopus Article | Citations
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