title: Human C-reactive protein binds activating Fcgamma receptors and protects myeloma tumor cells from apoptosis.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Michele
authors.initials: M
authors.lastname: Wezeman
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Jianfei
authors.initials: J
authors.lastname: Qian
authors.forename: Bo
authors.initials: B
authors.lastname: Wan
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
authors.forename: Long
authors.initials: L
authors.lastname: Yu
authors.forename: Qing
authors.initials: Q
authors.lastname: Yi
mesh_terms: 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