il17在大肠癌血管生成中的作用及机制研究-study on the role and mechanism of il17 in angiogenesis of colorectal cancer.docx

第三军医大学博士学位论文 第三军医大学博士学位论文 PAGE PAGE 4 IL-17 is associated with poor prognosis and promotes angiogenesis via stimulating VEGF production of cancer cells in colorectal carcinoma Abstract Background Colorectal carcinoma (CRC) is the third of the most common type of cancer in the world, and its incidence is increasing during last ten years. The present therapeutic methods such as surgery, chemotherapy and radiotherapy have their limits respectively. Each year, about 400,000 people suffer from CRC and about 293,500 die from it in China. Angiogenesis, stimulated by vascular endothelial growth factor (VEGF), is involved in the growth, local invasion and metastasis of tumor and with an unfavorable clinical course in CRC. Anti-VEGF agents, such as Bevacizumab, were added to the standard chemotherapy and improved the prognosis of patients with metastatic colorectal cancer. However, there may be some other potential angiogenic factors targeting angiogenesis in the treatment of CRC. An association between cancer development and inflammation has been proposed previously. More importantly, inflammation is considered as the seventh hallmark of cancer. Proinflammtory cytokines, such as IL-6 and IL-8, can activate inflammation and result in the chemoattraction of a variety of inflammatory cells. The inflammatory cells, such as T cells and tumor-associated macrophages, not only produce factors which can stimulate tumor proliferation and induce immune tolerance, but also are involved in angiogenesis by producing angiogenic factors, such as VEGF. IL-17 is a proinflammatory cytokine identified newly and produced mainly by activated CD4+ T helper cells which are termed Th17 cells. Previous studies have shown that IL-17-producing cells presented in gastric cancer, prostate cancer, non-small-cell lung carcinoma (NSCLC), hepatocellular carcinoma (HCC), breast cancer and ovarian cancer and IL-17 promoted angiogenesis in tumor models. However, the effects of IL-17 on angiogene