Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer
Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer
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DOI：
10.1007/s00262-014-1624-x
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发表时间：
2015-02-01
影响因子：
5.8
通讯作者：
Florholmen, Jon
中科院分区：
文献类型：
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作者：
Cui, Guanglin;Qi, Haili;Florholmen, Jon
大多数散发性结直肠癌（CRC）是由预先形成的腺瘤发展而来的。细胞因子参与腺瘤向结直肠癌的转变。白细胞介素-33（IL-33）是新近发现的一种促炎细胞因子，属于IL-1细胞因子家族，参与慢性炎症和癌症的发生发展。本研究的目的是评估IL-33/ST 2轴的动态过程中的正常结直肠腺瘤癌的进展，并探讨IL-33和ST 2表达与临床病理参数和预后的关系。结果显示：50例腺瘤组织中IL-33和ST 2的表达水平均显著高于30例正常对照组，而50例CRC组织中IL-33和STmRNA的表达水平均显著高于正常对照组，但低于腺瘤组织。进一步分析显示ST 2在CRC中的表达水平与肿瘤/淋巴结/转移（TNM）分期有关。对数秩检验显示，IL-33和ST 2表达水平均与CRC患者的总生存期无关。通过免疫组织化学证实了IL-33/ST 2在腺瘤和CRC组织中的表达增加，并且在肿瘤基质细胞和腺瘤/癌细胞中观察到。值得注意的是，在腺瘤和CRC的间质中发现IL-33阳性和ST 2阳性微血管密度增加。总之，IL-33/ST 2轴沿着大肠腺瘤-癌序列的表达增加可能通过该轴参与血管生成的调节而参与肿瘤转化。
Most sporadic colorectal cancers (CRCs) develop from preformed adenomas. Cytokines are involved in the transition from adenoma to CRC. Interleukin-33 (IL-33) is a newly discovered proinflammatory cytokine belonging to the IL-1 cytokine family and involved in the development of chronic inflammation and cancer. The aim of this study was to evaluate the dynamics of the IL-33/ST2 axis during the sequence of progression from normal colorectum to adenoma to carcinoma and to investigate the association of IL-33 and ST2 expression with clinicopathological parameters and prognosis. The results demonstrated that the levels of IL-33 and ST2 in adenomas (n = 50), determined by real-time PCR, were significantly higher than those of normal controls (n = 30); the levels of both IL-33/ST mRNA in CRCs (n = 50) were higher than in normal controls but lower than in adenomas. Further analysis revealed that the expression level of ST2 in CRCs was associated with tumor/node/metastasis (TNM) stage. The log-rank test showed that neither the IL-33 nor the ST2 expression level was correlated with overall survival in patients with CRC. The increased expression of IL-33/ST2 in adenomas and CRC tissues was confirmed by immunohistochemistry and was observed in both the tumor stromal cells and adenomatous/cancerous cells. Notably, increased densities of IL-33-positive and ST2-positive microvessels were found in the stroma of adenomas and CRCs. In conclusion, increased expression of the IL-33/ST2 axis along the colorectal adenoma-carcinoma sequence might be involved in the neoplastic transformation via the participation of this axis in the regulation of angiogenesis.