生物谷： 杜克大学医学中心Christopher Counter博士与其同事最近发现，IL-6是抵抗由Ras诱导的癌症的新靶标，这一成果刊登于新一期Genes & Development杂志。
Ras是一种关键的细胞内信号蛋白，与其它信号一起指导细胞生长和增殖。Ras致癌基因过表达或其生长-促进途径，是多种癌症特别是胰腺癌和肺癌的必经步骤。不幸的是，以Ras为靶标，抑制癌症的临床实验一直未成功。
Counter博士说，虽然Ras对癌症非常重要，但每次的以Ras为抑制癌症的直接靶标的尝试实验都以失败告终。他们此次希望找到一种能够抵抗Ras活性的成分，于是寻找在Ras被激活时，细胞开始分泌的其它蛋白，将这些蛋白作为候选的治疗剂。
在这些候选蛋白中，IL-6格外引人瞩目。IL-6是一种炎症细胞因子（生长因子），刺激免疫系统对损伤作出反应。Counter博士率领的研究小组证实在多种细胞中，Ras诱导IL-6分泌，IL-6通过刺激新血管生长而促进肿瘤发生。
临床前研究中，Counter博士与其同事通过抑制IL-6活性，成功抑制了肿瘤形成。当然，确定以IL-6为靶标的治癌试剂的疗效还需要进行深入研究。Counter博士说：“以Ras被激活时分泌的蛋白为靶标，为尝试利用有治疗作用的蛋白抑制Ras致癌信号的研究打开了一扇新的大门。”
原始出处:
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.
