Human C-reactive protein binds activating Fcgamma receptors and protects myeloma tumor cells from apoptosis.
Elevated levels of C-reactive protein (CRP) are present in many disease situations including malignancies and may contribute to the pathogenesis of cardiovascular disorders. This study was undertaken in a myeloma setting to determine whether CRP affects tumor cell growth and survival. We show that CRP enhanced myeloma cell proliferation under stressed conditions and protected myeloma cells from chemotherapy drug-induced apoptosis in vitro and in vivo. CRP binds activating Fcgamma receptors; activates PI3K/Akt, ERK, and NF-kappaB pathways; and inhibits caspase cascade activation induced by chemotherapy drugs. CRP also enhanced myeloma cell secretion of IL-6 and synergized with IL-6 to protect myeloma cells from chemotherapy drug-induced apoptosis. Thus, our results implicate CRP as a potential target for cancer treatment.
Yang
Jing
J
Department of Lymphoma and Myeloma, Division of Cancer Medicine, and the Center for Cancer Immunology Research, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.
Wezeman
Michele
M
Zhang
Xiang
X
Lin
Pei
P
Wang
Michael
M
Qian
Jianfei
J
Wan
Bo
B
Kwak
Larry W
LW
Yu
Long
L
Yi
Qing
Q
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002097:C-Reactive Protein / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D017452:Receptors, IgG / Q000378:metabolism*; D015398:Signal Transduction