Interleukin-17, produced by lymphocytes, promotes tumor growth and angiogenesis in a mouse model of breast cancer

Abstract

Previous studies have suggested that interleukin-17 (IL-17), an inflammatory cytokine expressed predominantly by Th17 cells, is highly expressed in tumor tissue and may help tumors to evade immune surveillance. In this study, the significance of IL-17 expression in the tumors of murine models of breast cancer was explored. BALB/c mice were injected with MA782/5S28102 or 4T1 breast cancer cell lines to establish breast tumors. The expression of IL-17 in tumor tissue was detected by western blotting 1 and 4 weeks later, which revealed that it increased with tumor progression (P<0.05). Additionally, tumor cells and tumor-infiltrating lymphocytes were isolated from tumor tissues and cultured for 5 days with stimulation by phorbol-12-myristate-13-acetate (PMA), anti‑CD3 antibody and anti-CD28 antibody. Culture media from stimulated tumor cells or tumor-infiltrating lymphocytes were harvested and their concentrations of IL-17 were tested by ELISA. Tumor cells secreted low levels of IL-17 into the media; however, lymphocytes from tumor tissues secreted high levels of IL-17, with 4T1 tumors secreting higher levels of IL-17 than MA782 tumors (P<0.05). To evaluate the effect of IL-17 on the proliferation of tumor cells, 4T1 cells were cultured in the presence or absence of recombinant IL-17 and cell numbers were counted on day 5 of culturing. Ectopic IL-17 did not promote the proliferation of tumor cells in vitro. To further understand the effect of IL-17 expression within tumors, 4T1 tumor-bearing mice were injected with recombinant IL-17 or saline via the tail vein. Tumor size was measured up to 21 days following the initial infusion of IL-17. IL-17 infusion resulted in an increased tumor volume and microvascular density (as measured by the immunohistochemical detection of CD34 expression in microvessels; P<0.05). Therefore, IL-17 expression within tumor tissues appears to originate from tumor-infiltrating lymphocytes and is likely to promote tumor growth by enhancing angiogenesis.

Immune regulatory cells and IL17-producing lymphocytes in patients with benign and malignant salivary gland tumors

“…It has also been reported that the prevalence of Th17 cells, as well as ROR␥t expression are diminished among PBMCs of the patients with NSCLC [19,38]. Contrary to these findings, other investigations suggested that Th17 cells may induce angiogenesis and participate in pro-tumorigenic processes associated with tumor growth [41][42][43][44]. Consistently some studies indicated that the percentage of these cells is increased in the peripheral blood of the patients with uterine cervical cancer (UCC), HNSCC and pancreatic cancer [24,45,46].…”

T cells, mast cells and microvascular density in diffuse large B cell lymphoma

“…In this Moreover, various T cell subsets have been implicated in angiogenesis, including Tregs correlation with MVD in other malignancies such as endometrial and breast carcinoma [20,21] and Th17 through infusion of IL-17 in mouse models of breast carcinoma, which may accelerate the progression of tumors by promoting angiogenesis [22]. Tregs may contribute to tumor angiogenesis both indirectly and directly by suppressing Th1 effector T cells that release angiostatic cytokines like TNF-a and interferon gamma (IFN-c) and by releasing high levels of vascular endothelial growth factor (VEGF), which promote capillary tube formation in vitro, respectively [23].…”

IL-17A Produced by γδ T Cells Promotes Tumor Growth in Hepatocellular Carcinoma

“…However, other reports have suggested potent protumor functions for IL-17A and IL-17A-producing cells. IL-17A overexpression in tumor cell lines promotes angiogenesis and tumor growth in immunodeficient mice (10), and IL-17A can promote tumor growth by enhancing angiogenesis in immunocompetent hosts (11). IL-17A can induce IL-6 production, which in turn promotes tumor growth in a Stat-3-dependent pathway (12).…”