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

Sci Signal 2017 Dec 12;10(509). Epub 2017 Dec 12.

Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

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.

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http://dx.doi.org/10.1126/scisignal.aan6282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827954PMC
December 2017
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C-reactive protein and beta-2 microglobulin produce a simple and powerful myeloma staging system
Bataille et al.
Blood 1992
Serum immunoreactive interleukin-6 and C-reactive protein levels in patients with multiple myeloma at diagnosis
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Br. J. Haematol. 1994

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