261) Inflammatory cytokines, components of cancer stem cells (CSCs) niche, could affect the characteristics of CSCs such as self-renewal and metastasis. |
PMID:24362529 DOI:10.1038/onc.2013.537 |
2015 Oncogene |
* Interleukin-17 produced by tumor microenvironment promotes self-renewal of CD133+ cancer stem-like cells in ovarian cancer. |
- Inflammatory cytokines, components of cancer stem cells (CSCs) niche, could affect the characteristics of CSCs such as self-renewal and metastasis. Interleukin-17 (IL-17) is a new pro-inflammatory cytokine mainly produced by T-helper (Th17) cells and macrophages. The effects of IL-17 on the characteristics of CSCs remain to be explored. Here we first demonstrated a role of IL-17 in promoting the self-renewal of ovarian CD133(+) cancer stem-like cells (CSLCs). We detected IL-17-producing cells (CD4(+) cells and CD68(+) macrophages) in the niche of CD133(+)CSLCs. Meanwhile, there was IL-17 receptor expression on CD133(+)CSLCs derived from A2780 cell line and primary ovarian cancer tissues. By recombinant human IL-17 stimulation and IL-17 transfection, the growth and sphere formation capacities of ovarian CD133(+)CSLCs were significantly enhanced in a dose-dependent manner. Moreover, ovarian CD133(+)CSLCs transfected with IL-17 showed greater tumorigenesis capacity in nude mice. These data suggest that IL-17 promoted the self-renewal of ovarian CD133(+)CSLCs. Further investigation through gene profiling revealed that the stimulation function of IL-17 on self-renewal of ovarian CD133(+)CSLCs might be mediated by the nuclear factor (NF)-κB and p38 mitogen-activated protein kinases (MAPK) signaling pathway. NF-κB and p38 MAPK were activated by IL-17. More importantly, IL-17-promoted self-renewal was inhibited by specific inhibitors of NF-κB and p38 MAPK. Taken together, our data indicate that IL-17 contributed to ovarian cancer malignancy through promoting the self-renewal of CD133(+)CSLCs and that IL-17 and its signaling pathway might serve as therapeutic targets for the treatment of ovarian cancer. |
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