Soluble IL-33 receptor sST2 inhibits colorectal cancer malignant growth by modifying the tumour microenvironment.
Soluble IL-33 receptor sST2 inhibits colorectal cancer malignant growth by modifying the tumour microenvironment.
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DOI：
10.1038/ncomms13589
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发表时间：
2016-11-24
影响因子：
16.6
通讯作者：
Takenaga, Keizo
中科院分区：
文献类型：
--
作者：
Akimoto, Miho;Maruyama, Riruke;Takamaru, Hiroyuki;Ochiya, Takahiro;Takenaga, Keizo
白细胞介素-33（IL-33）最近被证明参与炎症性肿瘤微环境和结直肠癌（CRC）的进展。我们在这里报告的表达水平的sST 2，可溶性形式的IL-33受体（ST 2L），是负相关的恶性生长的CRC。与低转移性人和小鼠CRC细胞相比，sST 2在高转移性细胞中下调。sST 2在低转移细胞中的敲低增强肿瘤生长、转移和肿瘤血管生成，而其在高转移细胞中的过表达抑制这些过程。循环和瘤内给予sST 2-Fc融合蛋白可减少高转移性CRC小鼠的肿瘤生长、转移性扩散和肿瘤血管生成。在机制上，sST 2抑制IL-33诱导的血管生成、Th 1-和Th 2-应答、巨噬细胞浸润和巨噬细胞M2 a极化。总之，我们发现sST 2通过改变肿瘤微环境负调节肿瘤生长和CRC转移扩散。因此，IL-33/ST 2L轴可能是CRC的潜在治疗靶点。 IL-33是一种促炎细胞因子，在结直肠癌中发挥作用。在这里，作者表明，循环肿瘤衍生的sST 2，一种IL-33诱饵受体，通过抑制Th 1/Th 2极化，巨噬细胞浸润和血管生成来延迟结直肠癌细胞的生长和进展。
Interleukin-33 (IL-33) was recently shown to be involved in the inflammatory tumour microenvironment and the progression of colorectal cancer (CRC). We report here that the expression level of sST2, a soluble form of the IL-33 receptor (ST2L), is inversely associated with the malignant growth of CRC. sST2 is downregulated in high-metastatic cells compared with low-metastatic human and mouse CRC cells. Knockdown of sST2 in low-metastatic cells enhances tumour growth, metastasis and tumour angiogenesis, whereas its overexpression in high-metastatic cells suppresses these processes. Circulating and intratumourally administered sST2-Fc fusion protein reduce tumour growth, metastatic spread and tumour angiogenesis in mice bearing high-metastatic CRC. Mechanistically, sST2 suppresses IL-33-induced angiogenesis, Th1- and Th2-responses, macrophage infiltration and macrophage M2a polarization. In conclusion, we show that sST2 negatively regulates tumour growth and the metastatic spread of CRC through modification of the tumour microenvironment. Thus, the IL-33/ST2L axis may be a potential therapeutic target in CRC. IL-33 is a pro-inflammatory cytokine with a role in colorectal cancer. Here, the authors show that circulating tumour-derived sST2, an IL-33 decoy receptor, delayed the growth and progression of colorectal cancer cells by inhibiting Th1/Th2 polarization, macrophage infiltration and angiogenesis.
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影响因子：
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