Human C-reactive protein binds activating Fcγ receptors and protects myeloma tumor cells from apoptosis
Human C-reactive protein binds activating Fcγ receptors and protects myeloma tumor cells from apoptosis
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DOI：
10.1016/j.ccr.2007.08.008
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发表时间：
2007-09-01
期刊：
影响因子：
50.3
通讯作者：
Yi, Qing
中科院分区：
文献类型：
--
作者：
Yang, Jing;Wezeman, Michele;Yi, Qing
C-反应蛋白（CRP）水平升高存在于许多疾病情况下，包括恶性肿瘤，并可能导致心血管疾病的发病机制。这项研究是在骨髓瘤背景下进行的，以确定CRP是否影响肿瘤细胞的生长和存活。我们发现，CRP增强骨髓瘤细胞在应激条件下的增殖和保护骨髓瘤细胞从化疗药物诱导的凋亡在体外和体内。CRP结合活化Fc γ受体;活化PI 3 K/Akt、ERK和NF-κ B通路;并抑制化疗药物诱导的半胱天冬酶级联活化。CRP还促进骨髓瘤细胞分泌IL-6，并与IL-6协同保护骨髓瘤细胞免受化疗药物诱导的凋亡。因此，我们的研究结果暗示CRP作为癌症治疗的潜在靶点。
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 Fc gamma receptors; activates PI3K/Akt, ERK, and NF-kappa B 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.