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Sci Signal. 2017 Dec 12;10(509). pii: eaan6282. doi: 10.1126/scisignal.aan6282.

C-reactive protein promotes bone destruction in human myeloma through the CD32-p38 MAPK-Twist axis.

Author information

1
Guangzhou Key Laboratory of Translational Medicine on Malignant Tumor Treatment, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, China. yiq@ccf.org jiyang@mdanderson.org.
2
Department of Lymphoma/Myeloma, Division of Cancer Medicine, and the Center for Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
3
Department of Physiology and Pathology, Tianjin Medical University, Tianjin 300070, China.
4
Department of Hematopathology, Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
5
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
6
Department of Hematology, The Myeloma and Lymphoma Center, Changzheng Hospital, The Second Military Medical University, Shanghai 200085, China.
7
Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Houston, TX 77030, USA.
8
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. yiq@ccf.org jiyang@mdanderson.org.

Abstract

Bone destruction is a hallmark of myeloma and affects 80% of patients. Myeloma cells promote bone destruction by activating osteoclasts. In investigating the underlying mechanism, we found that C-reactive protein (CRP), a protein secreted in increased amounts by hepatocytes in response to myeloma-derived cytokines, activated myeloma cells to promote osteoclastogenesis and bone destruction in vivo. In mice bearing human bone grafts and injected with multiple myeloma cells, CRP bound to surface CD32 (also known as FcγRII) on myeloma cells, which activated a pathway mediated by the kinase p38 MAPK and the transcription factor Twist that enhanced the cells' secretion of osteolytic cytokines. Furthermore, analysis of clinical samples from newly diagnosed myeloma patients revealed a positive correlation between the amount of serum CRP and the number of osteolytic bone lesions. These findings establish a mechanism by which myeloma cells are activated to promote bone destruction and suggest that CRP may be targeted to prevent or treat myeloma-associated bone disease in patients.

PMID:
29233917
PMCID:
PMC5827954
DOI:
10.1126/scisignal.aan6282
[Indexed for MEDLINE]
Free PMC Article

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