Our aim was to discover the role of IL-17, CXCR2 ligands, and cancer-associated neutrophils in chemotherapy resistance and metastasis in breast cancer.
Our analysis showed that both MIF and IL-17A were associated with increased risk of breast cancer (OR 3.85 CI 95% 1.98-7.50 and OR 4.51 95% 1.83-11.15, respectively), higher in aggressive subtypes Luminal B, HER2 and TN.
The authors previously demonstrated that high stimulating conditions (sub-minimal IL-17, 0.1 ng/ml, synergized with high salt, Δ0.05 M NaCl) promote breast cancer cell proliferation and CXCR4 expression through upregulation of salt-inducible kinase (SIK)-3.
In the present article, we review the accumulating evidences about the roles of IL-17 in BC and discuss whether this family of cytokines could be a new target in anticancer treatments.
The IL17 family consist of 6 protein members, among them IL17B and its receptor, and IL17RB signaling pathway plays a key role in development and progression of breast cancer, and targeting this signaling pathway or its specific downstream mediators by a chemotherapy drug and small interfering RNA interference is a potentially novel therapeutic pathway for inhibition of this disease.
Thus, our study established a pro-tumor role of IL-17A in promoting tumor immune escape and supports the development of a novel cytokine immunotherapy against breast cancer.
Interleukin-17 (IL-17) is a critical pro-inflammatory cytokine, which has been demonstrated to promote development of prostate cancer, colon cancer, skin cancer, breast cancer, lung cancer and pancreas cancer.
In this report, using three breast cancer-related cell lines, we determined the molecular basis of the potential synergistic inflammatory effect of sodium chloride (NaCl) with interleukin-17 (IL-17).
Investigation of the molecular signaling following stimulation of human breast cancer cell lines with IL-17A and IL-17E showed that both cytokines induced the phosphorylation of c-RAF, ERK1/2 and p70 S6 Kinase were involved in the proliferation and survival of tumor cells.
We further established that recombinant IL-17A recruits the MAPK pathway by upregulating phosphorylated ERK1/2 in human breast cancer cell lines thereby promoting proliferation and resistance to conventional chemotherapeutic agents such as docetaxel.
We genotyped three single-nucleotide polymorphisms (SNPs) in IL-17A (rs2275913, rs3819025 and rs3748067) and five SNPs in IL-17F (rs7771511, rs9382084, rs12203582, rs1266828 and rs763780) to determine the haplotypes in 491 women with breast cancer and 502 healthy individuals.
Analysis of human breast cancer transcriptome databases showed a strong association between IL-17 gene expression and poor outcome in lymph node positive, estrogen receptor negative or luminal B subtypes suggesting potential therapeutic approaches.