No abstract

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.

Lung cancer is the leading cause of cancer‑related mortality worldwide. The complement component 3 (C3) is a central protein of the complement system, expressed in numerous cancer tissues and considered crucial for tumor progression. This study aimed to investigate the prognostic value of C3 in non‑small cell lung cancer (NSCLC) and the underlying mechanisms. We used immunohistochemistry to observe the expression of C3 in malignant pulmonary lesion specimens from biopsy of 80 patients with NSCLC at stages I‑III, who underwent lobectomy. We further assessed the correlation between C3 expression and a number of clinical features, as well as its prognostic value. To investigate the mechanism by which C3 exerts its effects, the correlation of C3 expression to T lymphocyte infiltration was also assessed. There was no significant correlation between the C3 level and clinical features such as gender, smoking status, degree of differentiation, histological type and malignant tumor stage based on the TNM classification system, while a significant correlation was found to age. However, analysis of overall survival (OS) and disease‑free survival (DFS) rates showed that low C3 expression was related to poor prognosis. Univariate survival analysis revealed that C3 level and TNM stage are independent prognostic factors. Multivariate analysis demonstrated that the low level of C3 and TNM stage are also associated with poor prognosis. Furthermore, in tissues from biopsies, the C3 level positively correlated to the number of infiltrated CD4+ and CD8+ T lymphocytes (P<0.01). These findings indicate that C3 is a valuable marker for prognostic evaluation of NSCLC and may be considered as a therapeutic target for the treatment of lung cancer.