Objective: Haptoglobin (Hp) is an acute-phase protein secreted by the liver; its concentration increases rapidly during infection, inflammation, and tumor formation. It has been reported that the level of Hp α alleles is altered in the serum of patients with head and neck squamous cell carcinoma (HNSCC), and the cellular level of Hp is strongly associated with the recurrence rate of HNSCC in patients. In the present study, the regulated mechanism of Hp expression was explored.
Materials and methods: We first identified the genetic polymorphism of Hp by PCR. The expression of Hp isoforms was determined through Western Blotting analysis. With the JAK specific inhibitors, the clear regulation mechanism was explored.
Results: We observed that Hp exhibited variant polymorphisms in different cells. We found that interleukin-6 (IL-6) induced the expressions of Hp α2 in FaDu cells, and Hp α1 in SCC4 cells. Furthermore, the phosphorylated level of STAT3 was elevated with IL-6 treatment. Janus-associated kinase 2 (JAK-2) inhibitor, WP1066, reduced the phosphorylation of STAT3 after IL-6 induction, leading to the downregulation of Hp expression.
Conclusions: The expression of Hp was increased via IL-6 induction through the activation of the transcription factor STAT3 in HNSCC cells.
Keywords: STAT3; haptoglobin; head and neck squamous cell carcinoma; interleukin-6.
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.