Interleukin-1a regulated the expression of proinflammatory cytokines in cancer-associated fibroblasts

• Main Authors: WANG,HSIU-HUA, 王秀華
• Other Authors: Tyan Shiaw-Wei
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/5zbcn7

碩士 === 嘉南藥理大學 === 生物科技系 === 103 === 　Cancer-associated fibroblasts (CAFs) have been shown to secrete high levels of proinflammatory cytokines. These proinflammatory cytokines, such as interleukin-6 (IL-6) and IL-8, were reported to assist cancer cell proliferation, angiogenesis and invasion. However, the mechanisms by which fibroblasts become proinflammatory ones during cancer progression are still not known. In this study, I found that through co-culturing with breast cancer cells, breast normal tissue-associated fibroblasts (NAFs) obtained persistent activity for expressing high levels of proinflammatory factors, including IL-1a, IL-1b, IL-6 and IL-8. IL-1a and IL-1b were respectively reported to play a role in induction of IL-6 and IL-8, so I tested the hypothesis that breast cancer cells might induce IL-6 and IL-8 expression in NAFs via an IL-1a or IL-1b signaling pathway. By using an IL-1a neutralizing antibody, I found that abolishment of IL-1a activity completely repressed the enhanced IL-8 expression and partially reduced the enhanced IL-1b and IL-6 expression in NAFs that were pre-cocultured with breast cancer MDA-MB-468 cells. However, an IL-1b neutralizing antibody had no effect on the expression of these cytokines. Furthermore, the treatment of an IL-1a neutralizing antibody also reduced the enhanced IL-1b, IL-6 and IL-8 expression in CAFs. These results suggested that IL-1a may mediate induction of IL-1b, IL-6 and IL-8 expression in cancer-associated fibroblasts. An IL-1a signaling pathway in stromal cells may be a target for prevention of breast cancer development and progression.