Cancer Cell：人类C反应蛋白和骨髓瘤细胞生长有关
生物谷报道： 科学家最近发现一种常见的炎症标记分子在人类癌症发展过程中起到了重要作用。研究结果发表在9月份的Cancer Cell上，文章认为C反应蛋白（CRP）或许是治疗癌症的新目标。
CRP蛋白由肝脏产生，并在炎症反应过程中被分泌出来，以对炎症中的细胞因子（cytokine）IL-6作出反应。在患有感染、炎症疾病、某些心血管疾病和包括多发性骨髓瘤（MM）在内的恶性肿瘤患者体内，其血液中CRP浓度都会上升。来自M. D. Anderson癌症中心的Qing Yi和Jing Yang博士及同事设计了一系列实验来分析人类CRP是否会影响MM肿瘤细胞的产生和存活。
科学家发现将CRP按照MM病人体内观察到的浓度加入培养细胞中将促进骨髓瘤细胞增生，并且保护它们免受化疗和IL-6引起的细胞凋亡影响。CRP的这种保护作用在患骨髓瘤的老鼠模型中也得到了确认。
研究人员继续分析了造成CRP对骨髓瘤细胞保护作用的潜在细胞信号路径。结果证明CRP促进了IL-6的分泌，激活了Fcg受体、PI3K/Akt、ERK以及NF-kB通路，并且抑制了化疗药物引发的caspase蛋白联级放大。除此之外，CRP还能和IL-6共同作用，加强防止骨髓细胞免于凋亡的作用。
以上结果证明CRP不仅是MM的标记分子，并且对于骨髓瘤细胞的存活起到了关键的调节作用。Yi表示：“CRP避免了化疗药物作用下骨髓瘤细胞的凋亡，并激发骨髓瘤细胞分泌更多的IL-6，从而为癌细胞提供了更多保护，并激发肝细胞分泌更多CRP。因此，CRP能作为打破骨髓瘤恶性循环的治疗目标，从而提高现有治疗手段的效果。” （教育部科技发展中心）
原文链接：http://www.physorg.com/news108648292.html
原始出处:
Article
Jing Yang,1 Michele Wezeman,1 Xiang Zhang,1 Pei Lin,2 Michael Wang,1 Jianfei Qian,1 Bo Wan,3 Larry W. Kwak,1 Long Yu,3 and Qing Yi1,3,
1 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
2 Department of Hematopathology, Division of Pathology, and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
3 State Key Laboratory of Genetics, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433, China
Corresponding author
Qing Yi
qyi@mdanderson.org
Summary
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 Fcγ receptors; activates PI3K/Akt, ERK, and NF-κB 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.
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