生物谷： 杜克大學(xué)醫(yī)學(xué)中心Christopher Counter博士與其同事最近發(fā)現(xiàn)，IL-6是抵抗由Ras誘導(dǎo)的癌癥的新靶標(biāo),，這一成果刊登于新一期Genes & Development雜志,。
Ras是一種關(guān)鍵的細(xì)胞內(nèi)信號蛋白，與其它信號一起指導(dǎo)細(xì)胞生長和增殖,。Ras致癌基因過表達(dá)或其生長-促進(jìn)途徑,，是多種癌癥特別是胰腺癌和肺癌的必經(jīng)步驟。不幸的是,，以Ras為靶標(biāo),，抑制癌癥的臨床實(shí)驗(yàn)一直未成功。
Counter博士說,，雖然Ras對癌癥非常重要,，但每次的以Ras為抑制癌癥的直接靶標(biāo)的嘗試實(shí)驗(yàn)都以失敗告終。他們此次希望找到一種能夠抵抗Ras活性的成分,，于是尋找在Ras被激活時,，細(xì)胞開始分泌的其它蛋白，將這些蛋白作為候選的治療劑,。
在這些候選蛋白中，IL-6格外引人矚目,。IL-6是一種炎癥細(xì)胞因子（生長因子）,，刺激免疫系統(tǒng)對損傷作出反應(yīng)。Counter博士率領(lǐng)的研究小組證實(shí)在多種細(xì)胞中,，Ras誘導(dǎo)IL-6分泌,，IL-6通過刺激新血管生長而促進(jìn)腫瘤發(fā)生。
臨床前研究中,，Counter博士與其同事通過抑制IL-6活性,，成功抑制了腫瘤形成。當(dāng)然,，確定以IL-6為靶標(biāo)的治癌試劑的療效還需要進(jìn)行深入研究,。Counter博士說：“以Ras被激活時分泌的蛋白為靶標(biāo)，為嘗試?yán)糜兄委熥饔玫牡鞍滓种芌as致癌信號的研究打開了一扇新的大門,。”
原始出處:
GENES & DEVELOPMENT 21:1714-1719, 2007
Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis
Brooke Ancrile, Kian-Huat Lim, and Christopher M. Counter1
Department of Pharmacology and Cancer Biology, Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA
Ras is mutated to remain in the active oncogenic state in many cancers. As Ras has proven difficult to target therapeutically, we searched for secreted, druggable proteins induced by Ras that are required for tumorigenesis. We found that Ras induces the secretion of cytokine IL6 in different cell types, and that knockdown of IL6, genetic ablation of the IL6 gene, or treatment with a neutralizing IL6 antibody retard Ras-driven tumorigenesis. IL6 appears to act in a paracrine fashion to promote angiogenesis and tumor growth. Inhibiting IL6 may therefore have therapeutic utility for treatment of cancers characterized by oncogenic Ras mutations.
[Keywords: Ras; oncogene; IL6; cytokine; cancer]
Received March 6, 2007; revised version accepted June 8, 2007.
