Interleukin-8 and its receptor CXCR2 in the tumour microenvironment promote colon cancer growth, progression and metastasis.
Interleukin-8 and its receptor CXCR2 in the tumour microenvironment promote colon cancer growth, progression and metastasis.
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DOI：
10.1038/bjc.2012.177
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发表时间：
2012-05-22
影响因子：
8.8
通讯作者：
Hong, Y-K
中科院分区：
文献类型：
--
作者：
Lee, Y. S.;Choi, I.;Ning, Y.;Kim, N. Y.;Khatchadourian, V.;Yang, D.;Chung, H. K.;Choi, D.;LaBonte, M. J.;Ladner, R. D.;Venkata, K. C. Nagulapalli;Rosenberg, D. O.;Petasis, N. A.;Lenz, H-J;Hong, Y-K
结直肠癌（CRC）是美国的主要死亡原因。肿瘤上和肿瘤微环境中白细胞介素-8（IL-8）和CXCR 2水平的升高与患者的CRC生长、进展和复发相关。在这里，我们的目的是评估组织微环境编码的IL-8和CXCR 2对结肠癌进展和转移的影响。一种新的免疫缺陷，皮肤特异性IL-8表达转基因模型的产生，以评估结肠癌的生长和转移。将同基因小鼠结肠癌细胞移植到CXCR 2敲除（KO）小鼠中，以研究微环境中CXCR 2对癌症生长的贡献。血清和肿瘤微环境中IL-8水平的升高显著增强了人和小鼠结肠癌细胞的生长，增加了肿瘤周围的血管生成，并且还促进了癌细胞外渗到肺和肝中。CXCR 2 KO小鼠的肿瘤生长受到抑制，肿瘤血管生成显著减少，肿瘤坏死增加。肿瘤微环境中IL-8表达的增加促进了结肠癌的生长和转移。此外，肿瘤微环境中缺乏其受体CXCR 2可以阻止结肠癌细胞的生长。总之，我们的研究证明了肿瘤微环境编码的IL-8/CXCR 2在结肠癌发病机制中的关键作用，验证了该途径作为重要的治疗靶点。
Colorectal cancer (CRC) is a leading cause of death in the United States. Increased level of interleukin-8 (IL-8) and CXCR2 on tumours and in the tumour microenvironment has been associated with CRC growth, progression and recurrence in patients. Here, we aimed to evaluate the effects of tissue microenvironment-encoded IL-8 and CXCR2 on colon cancer progression and metastasis. A novel immunodeficient, skin-specific IL-8-expressing transgenic model was generated to evaluate colon cancer growth and metastasis. Syngeneic mouse colon cancer cells were grafted in CXCR2 knockout (KO) mice to study the contribution of CXCR2 in the microenvironment to cancer growth. Elevated levels of IL-8 in the serum and tumour microenvironment profoundly enhanced the growth of human and mouse colon cancer cells with increased peri-tumoural angiogenesis, and also promoted the extravasation of the cancer cells into the lung and liver. The tumour growth was inhibited in CXCR2 KO mice with significantly reduced tumour angiogenesis and increased tumour necrosis. Increased expression of IL-8 in the tumour microenvironment enhanced colon cancer growth and metastasis. Moreover, the absence of its receptor CXCR2 in the tumour microenvironment prevented colon cancer cell growth. Together, our study demonstrates the critical roles of the tumour microenvironment-encoded IL-8/CXCR2 in colon cancer pathogenesis, validating the pathway as an important therapeutic target.
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影响因子：
2.1
作者：
Gordon, MA;Gil, J;Lenz, HJ
通讯作者：
Lenz, HJ
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Shimosegawa, T
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Strieter, RM
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Chung, DC