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Interleukin-17 produced by tumor microenvironment promotes self-renewal of CD133+ cancer stem-like cells in ovarian cancer

Xiang, T ; Long, H ; He, L ; Han, X ; Lin, K ; Liang, Z ; Zhuo, W ; Xie, R ; Zhu, B

Oncogene, 2015-01, Vol.34 (2), p.165-176 [Periódico revisado por pares]

England: Nature Publishing Group

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Interleukin-17 produced by tumor microenvironment promotes self-renewal of CD133+ cancer stem-like cells in ovarian cancer
Autor: Xiang, T ; Long, H ; He, L ; Han, X ; Lin, K ; Liang, Z ; Zhuo, W ; Xie, R ; Zhu, B
Assuntos: AC133 Antigen ; Animals ; Antigens, CD - biosynthesis ; Antigens, CD - immunology ; Cancer ; CD4 antigen ; Cell Line, Tumor ; Cell self-renewal ; Cytokines ; Female ; Gene Expression Profiling ; Glycoproteins - biosynthesis ; Glycoproteins - immunology ; Helper cells ; Heterografts ; Humans ; Inflammation ; Interleukin 17 ; Interleukin-17 - biosynthesis ; Interleukin-17 - genetics ; Interleukin-17 - immunology ; Kinases ; Lymphocytes T ; Macrophages ; Malignancy ; MAP kinase ; Metastases ; Mice ; Mice, Nude ; Mice, SCID ; Neoplastic Stem Cells - immunology ; Neoplastic Stem Cells - pathology ; NF-κB protein ; Ovarian cancer ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - immunology ; Ovarian Neoplasms - pathology ; Peptides - immunology ; Signal transduction ; Stem cell transplantation ; Stem cells ; Therapeutic applications ; Transfection ; Tumor Microenvironment - immunology ; Tumorigenesis
É parte de: Oncogene, 2015-01, Vol.34 (2), p.165-176
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: 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.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Interleukin-17 produced by tumor microenvironment promotes self-renewal of CD133+ cancer stem-like cells in ovarian cancer

Xiang, T ; Long, H ; He, L ; Han, X ; Lin, K ; Liang, Z ; Zhuo, W ; Xie, R ; Zhu, B

England: Nature Publishing Group

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