IL-17 is associated with poor prognosis and promotes angiogenesis via stimulating VEGF production of cancer cells in colorectal carcinoma |
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Authors: | Jiankun Liu Yuzhong Duan Xiaoming Cheng Xi Chen Wei Xie Haixia Long Zhihua Lin Bo Zhu |
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Affiliation: | aInstitute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, PR China;bInstitute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, PR China;cCollege of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400050, PR China |
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Abstract: | IL-17, which exerts strong pro-inflammatory effects, has emerged as an important mediator in inflammation-associated cancer. However, the characteristics of IL-17-producing cells, the relevance of IL-17 to clinical parameters and its function in the development and progression of colorectal carcinoma still remain to be explored. In the present study, we first found the levels of IL-17 producing cells were significantly increased in the tumor regions of samples from colorectal carcinoma patients compared with non-tumor regions. Confocal microscopic analysis showed co-staining of IL-17 with CD4 and CD68, indicating IL-17 in colorectal carcinoma was expressed by macrophage and Th17. High expression of IL-17 was associated with high microvessel density. Univariate and multivariate analysis revealed that IL-17 was an independent prognostic factor for overall survival. To explore the underlying mechanisms of IL-17 in angiogenesis, we used PCR-array to find pro-angiogenic factor in cancer cells specifically induced by IL-17, then validated VEGF as one of factors in IL-17-mediated angiogenesis with the use of quantitative RT-PCR, ELISA and VEGF immunohistochemistry. Our results propose IL-17 as a novel indicator of prognosis in the patients with colorectal carcinoma and could serve as a novel therapeutic target for colorectal carcinoma, furthermore our results indicate that IL-17 producing cells may facilitate development of colorectal carcinoma by fostering angiogenesis via promote VEGF production from cancer cells. |
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Keywords: | IL-17 VEGF Colorectal carcinoma Prognosis |
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