The medium was exchanged (0.5% Ethyl dirazepate FBS). metastatic potential of colon cancer cell line (HT-29) because it can secrete autocrine IL-1, significantly enhanced angiogenesis compared with low liver metastatic cell line (CaCo-2) ( em P /em 0.01), which does not secrete IL-1. On the contrary, blockage of autocrine IL-1 by IL-1RA might significantly decrease metastatic potential of colon carcinoma cells through downregulation of IL-1/PI3K/NF-B pathway. Conclusion IL-1 receptor antagonist (IL-1RA) is an important inhibitor in metastatic process of colon carcinoma cell. Based on Ethyl dirazepate the above results, we suggest that IL-1RA may be a promising new therapeutic approach in inhibiting colon cancer with IL-1-producing patients. strong class=”kwd-title” Keywords: interleukin receptor antagonist, hepatocyte growth factor, metastasis, angiogenesis, colon cancer, IL-1RA, HGF, angiogenesis, colon carcinoma Introduction Colorectal carcinoma is one of the deadliest cancers due to its high propensity to metastatic potential. It accounts for ~1 million new incidence of colon cancer cases and causes a half million deaths annually worldwide.1C3 The main treatment of colorectal cancer at present are surgical radical operation, chemotherapy, radiotherapy, and targeted therapy.4 There have not been highly effective approaches against metastasis of colorectal cancer so far. Recently, researching around the microenvironment of solid tumors shows that chemokines and their receptors act as key function in cancer metastatic process, and chemokines play their specific role in the regulation of angiogenesis, activation of a tumor-specific immune response, and inducing proliferation of tumor cell in an autocrine or paracrine fashion.5C8 Development of new blood vessels is the critical path in the progressive growth of solid tumor. Angiogenesis is critical for metastasis of carcinoma cell, which not only carries oxygen and essential nutrients to the tumor, but also facilitates the spread and proliferation of cancer cells. 9 The says of angiogenesis are essential for both tumor cell growth and metastasis. Angiogenesis is usually a complicated and multistep process involving extracellular matrix remodeling, migration, and proliferation of Ethyl dirazepate endothelial cell and capillary vessel formation.10 These processes depend around the production of Ethyl dirazepate angiogenic factors secreted by both tumor and stromal cells.11 Angiogenesis provides a gateway for the tumor cells entering the circulation and metastasizing to distant organs, such as liver or lung. Thus, it is a critical step in tumor cell metastasis. Interleukin (IL)-1 is an important inflammatory cytokine. It is produced by cancer cells, such as colon, pancreas, lung, ovary, and gastric cancer. IL-1 can induce the expression of adhesion molecules in vascular endothelial cells and enhance expression of proteases in pancreatic cancer.12,13 Recent research showed that IL-1 was highly expressed in tumor environment and was secreted by tumor cells or stromal cells. IL-1 binds to the IL-1 receptor 1 (IL-1R1), which then forms a complex with the IL-1 receptor accessory protein (IL-1RAcP).10,25 It can stimulate the development of cancers. However, the underlying mechanism that IL-1 influences the tumor behaviors remains poorly characterized. Therefore, the associations between cells and IL-1 in tumor environment is not fully comprehended, especially critical is the exploration of the innate pathways of IL-1 regulating metastatic potential in tumor microenvironments.14 Hepatocyte growth factor (HGF), a kind of pleiotropic cytokine, acts as a highly specific mitogen for endothelial cells that regulates cell proliferation, invasiveness, survival, and tumor angiogenesis.15,16 MET proto-oncogene, receptor tyrosine kinase (c-Met) is the receptor for HGF. c-Met overexpression is usually associated with the proliferation, invasion and metastasis of cancer cells.17 HGF has been identified as a stromal cells-derived epithelial morphogen that induces branching tubular morphogenesis. The stromal cells-derived HGF plays an important role in cancer cells invasiveness and proliferation.18C20 Fibroblasts production of HGF has been regulated by IL-1, tumor necrosis factor (TNF), and basic fibroblast growth factor (bFGF), and leading to the enhanced invasion and proliferation ability of carcinoma cells.21 IL-1 receptor antagonist (IL-1RA) is an endogenous inhibitor of IL-1 that prevents the activation of IL-1 receptors by inhibiting. IL-1RA is usually connected with a variety of diseases, including cardiovascular disease, type II diabetes, carcinoma and joint diseases.22 IL-1RA has been shown to improve the symptoms of the disease in the treatment of pre-clinical animal PTOA (posttraumatic osteoarthritis) models.23 IL-1RA is also a promising drug for the treatment Rabbit Polyclonal to TNF14 of stroke. It is reported that it may improve the immune response in traumatic brain injury and subarachnoid hemorrhage.24 The authors should describe more.
