Cancer-associated fibroblasts (CAFs) have been shown to secrete high levels of proinflammatorycytokines. These proinflammatory cytokines, such asinterleukin-6 (IL-6) and IL-8, were reported to assistcancer cell proliferation, angiogenesis and invasion. However, the mechanisms by which fibroblasts become proinflammatory ones during cancer progression are still not known. Here, we showed that through co-culturing with breast cancer cells for at least three-four passages, breast normal tissue-associated fibroblasts (NAFs) obtained persistent activity for expressing high levels of proinflammatory factors, including IL-1, IL-1, IL-6 and IL-8. IL-1and IL-1were respectively reported to play a role in induction of IL-6 and IL-8, so we tested the hypothesis that breast cancer cells might induce IL-6 and IL-8 expression in NAFs via anIL-1or IL-1signaling pathway. By using an IL-1neutralizing antibody, we found that abolishment ofIL-1activity completely repressed the enhanced IL-8 expression and partially reduced the enhanced IL-1and IL-6 expression in NAFs that were pre-cocultured with breast cancer MDA-MB-468 cells. However, an IL-1neutralizing antibody had no effect on the expression of these cytokines. Furthermore, the treatment of an IL-1neutralizing antibody also reduced the enhanced IL-1, IL-6 and IL-8 expression in CAFs. These results suggested that IL-1may mediate induction of IL-1, IL-6 and IL-8 expression in cancer-associated fibroblasts. AnIL-1signaling pathway in stromalcells may be a target for prevention of breast cancer development and progression.
