Chemerin promotes invasion of oral squamous cell carcinoma cancer by stimulating IL-6/TNF-α production via STAT3 signaling pathway

Abstract

Aims: The primary hallmark of oral cancer is cervical lymph node metastases. Previously, we discovered that elevated serum chemerin levels were related to oral squamous cell carcinoma (OSCC) with lymph node metastases. However, the mechanisms by which chemerin promotes OSCC metastasis are unknown. In this work, we focused on inflammation to investigate the mechanisms of chemerin-mediated OSCC metastasis. Methods: Serum from 10 pairs of OSCC patients with and without cervical lymph node metastases was collected before surgery. A Luminex liquid suspension assay was used to quantify the concentration of 27 different types of cytokines. Chemerin and inflammatory factors were validated by ELISA in both blood serum and cell culture supernatant. The relationship between chemerin and inflammatory factors was analysed. Western blot was used to measure the amount of phosphorylated STAT3 protein expression. Migration and invasion were investigated using the transwell assay. Results: Compared with the group without metastases, the levels of IL-6 (P = 0.006), IL-15 (P = 0.020), GM-CSF (P = 0.036), RANTES (P = 0.032), TNF-α (P = 0.005) and VEGF (P = 0.006) were significantly higher in OSCC patients with metastases. Serum chemerin level was found to correlate significantly with IL-6, GM-CSF, TNF-α and VEGF. Furthermore, treatment with recombinant chemerin significantly induced the secretion of IL-6 and TNF-α via activation of the STAT3 signalling pathway in OSCC cells. An IL-6/TNF-α neutralising antibody also reduced chemerin-induced migration and invasion of OSCC cells. Conclusion: These finding suggested that chemerin contributed to OSCC development might be associated with increasing IL-6 and TNF-α through activation of the STAT3 pathway.