Interleukin-6 released by colon cancer-associated fibroblasts is critical for tumour angiogenesis: anti-interleukin-6 receptor antibody suppressed angiogenesis and inhibited tumour-stroma interaction.
Interleukin-6 released by colon cancer-associated fibroblasts is critical for tumour angiogenesis: anti-interleukin-6 receptor antibody suppressed angiogenesis and inhibited tumour-stroma interaction.
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DOI：
10.1038/bjc.2013.748
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发表时间：
2014-01-21
影响因子：
8.8
通讯作者：
Takeyama, H.
中科院分区：
文献类型：
--
作者：
Nagasaki, T.;Hara, M.;Nakanishi, H.;Takahashi, H.;Sato, M.;Takeyama, H.
关键词：
白细胞介素-6（IL-6）在癌症进展中具有重要作用，并且高水平的血浆IL-6与多种癌症的不良预后相关。还报道了肿瘤基质成纤维细胞对于癌症进展中的步骤（例如血管生成）是必需的。很少有报道成纤维细胞的作用和IL-6水平之间的相关性。在这项研究中，我们研究了癌间质成纤维细胞和IL-6之间的相关性，以及IL-6作为人类结肠癌治疗靶点的效用。采用实时荧光定量PCR和ELISA检测成纤维细胞和癌细胞系中IL-6和VEGF的表达水平。在血管生成模型和动物实验中测量抑制IL-6信号传导的抗血管生成作用。我们证明，从结肠癌中分离的基质成纤维细胞产生大量的IL-6，结肠癌细胞增强基质成纤维细胞产生IL-6。此外，IL-6增强成纤维细胞产生VEGF，从而诱导血管生成。在体内，靶向间质组织的抗IL 6受体抗体显示出比靶向异种移植癌细胞的抗IL 6受体抗体更大的抗肿瘤活性。癌间质成纤维细胞是结肠癌中IL-6的重要来源。由活化的成纤维细胞产生的IL-6通过刺激邻近的基质成纤维细胞诱导肿瘤血管生成。IL-6与间质成纤维细胞之间的关系为癌症治疗提供了新的途径。
Interleukin-6 (IL-6) has an important role in cancer progression, and high levels of plasma IL-6 are correlated with a poor prognosis in a variety of cancers. It has also been reported that tumour stromal fibroblasts are necessary for steps in cancer progression, such as angiogenesis. There have been few reports of a correlation between fibroblast actions and IL-6 levels. In this study, we examined the correlation between cancer stromal fibroblasts and IL-6 and the utility of IL-6 as a therapeutic target in human colon cancer. The expression levels of IL-6 and VEGF of fibroblasts and cancer cell lines were evaluated using real-time PCR and ELISA. The anti-angiogenic effect of inhibiting IL-6 signalling was measured in an angiogenesis model and animal experiment. We demonstrate that stromal fibroblasts isolated from colon cancer produced significant amounts of IL-6 and that colon cancer cells enhanced IL-6 production by stromal fibroblasts. Moreover, IL-6 enhanced VEGF production by fibroblasts, thereby inducing angiogenesis. In vivo, anti-IL6 receptor antibody targeting stromal tissue showed greater anti-tumour activity than did anti-IL6 receptor antibody targeting xenografted cancer cells. Cancer stromal fibroblasts were an important source of IL-6 in colon cancer. IL-6 produced by activated fibroblasts induced tumour angiogenesis by stimulating adjacent stromal fibroblasts. The relationship between IL-6 and stromal fibroblasts offers new approaches to cancer therapy.
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影响因子：
11.2
作者：
Liu S;Ginestier C;Ou SJ;Clouthier SG;Patel SH;Monville F;Korkaya H;Heath A;Dutcher J;Kleer CG;Jung Y;Dontu G;Taichman R;Wicha MS
通讯作者：
Wicha MS
影响因子：
8
作者：
Niu, GL;Wright, KL;Yu, H
通讯作者：
Yu, H
DOI：
10.1155/2011/765624
发表时间：
2011
期刊：
Arthritis
影响因子：
--
作者：
Hashizume M;Mihara M
通讯作者：
Mihara M
IL-6促进U251和T98G细胞系中胶质母细胞瘤细胞侵袭和血管生成
影响因子：
3.9
作者：
Liu, Qinglin;Li, Gang;Zhang, Jian
通讯作者：
Zhang, Jian
影响因子：
--
作者：
Hugo, Honor J.;Lebret, Stephanie;Ackland, M. Leigh
通讯作者：
Ackland, M. Leigh