生物谷報(bào)道： 科學(xué)家最近發(fā)現(xiàn)一種常見(jiàn)的炎癥標(biāo)記分子在人類癌癥發(fā)展過(guò)程中起到了重要作用。研究結(jié)果發(fā)表在9月份的Cancer Cell上,，文章認(rèn)為C反應(yīng)蛋白（CRP）或許是治療癌癥的新目標(biāo),。
CRP蛋白由肝臟產(chǎn)生，并在炎癥反應(yīng)過(guò)程中被分泌出來(lái),，以對(duì)炎癥中的細(xì)胞因子（cytokine）IL-6作出反應(yīng),。在患有感染、炎癥疾病,、某些心血管疾病和包括多發(fā)性骨髓瘤（MM）在內(nèi)的惡性腫瘤患者體內(nèi),，其血液中CRP濃度都會(huì)上升。來(lái)自M. D. Anderson癌癥中心的Qing Yi和Jing Yang博士及同事設(shè)計(jì)了一系列實(shí)驗(yàn)來(lái)分析人類CRP是否會(huì)影響MM腫瘤細(xì)胞的產(chǎn)生和存活,。
科學(xué)家發(fā)現(xiàn)將CRP按照MM病人體內(nèi)觀察到的濃度加入培養(yǎng)細(xì)胞中將促進(jìn)骨髓瘤細(xì)胞增生,，并且保護(hù)它們免受化療和IL-6引起的細(xì)胞凋亡影響。CRP的這種保護(hù)作用在患骨髓瘤的老鼠模型中也得到了確認(rèn),。
研究人員繼續(xù)分析了造成CRP對(duì)骨髓瘤細(xì)胞保護(hù)作用的潛在細(xì)胞信號(hào)路徑,。結(jié)果證明CRP促進(jìn)了IL-6的分泌，激活了Fcg受體,、PI3K/Akt,、ERK以及NF-kB通路，并且抑制了化療藥物引發(fā)的caspase蛋白聯(lián)級(jí)放大,。除此之外,，CRP還能和IL-6共同作用，加強(qiáng)防止骨髓細(xì)胞免于凋亡的作用,。
以上結(jié)果證明CRP不僅是MM的標(biāo)記分子,，并且對(duì)于骨髓瘤細(xì)胞的存活起到了關(guān)鍵的調(diào)節(jié)作用。Yi表示：“CRP避免了化療藥物作用下骨髓瘤細(xì)胞的凋亡,，并激發(fā)骨髓瘤細(xì)胞分泌更多的IL-6,，從而為癌細(xì)胞提供了更多保護(hù)，并激發(fā)肝細(xì)胞分泌更多CRP,。因此，CRP能作為打破骨髓瘤惡性循環(huán)的治療目標(biāo),，從而提高現(xiàn)有治療手段的效果,。” （教育部科技發(fā)展中心）
原文鏈接：http://www.physorg.com/news108648292.html
原始出處:
Cancer Cell, Vol 12, 252-265, 11 September 2007
Article
Human C-Reactive Protein Binds Activating Fcγ Receptors and Protects Myeloma Tumor Cells from Apoptosis
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
[email protected]
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.
