IFNγ induces JAK1/STAT1/p65 NFκB-dependent interleukin-8 expression in ovarian cancer cells, resulting in their increased migration

Interferon-gamma (IFN gamma) is a pleiotropic cytokine that has a crucial role in immune response and tumor immunity. Because of its anti-tumor effects, IFN gamma has been used in cancer treatment. However, IFN gamma also has tumor-promoting functions that are less well understood. Here, we show that IFN gamma induces expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (IL-8, CXCL8) in ovarian cancer (OC) cells. The IFN gamma-induced IL-8 expression is dependent on JAK1, STAT1, and p65 NF kappa B, and is associated with an increased occupancy of K314/315 acetylated p65 NF kappa B and Ser-727 phosphorylated STAT1 at the IL-8 promoter. Neutralization of IL-8 using anti-IL-8 antibody reduces IFN gamma-induced migration of OC cells, and their invasion ability in 3D spheroids. Together, these findings identify IL-8 as a novel target induced by IFN gamma/JAK1/STAT1/ p65 NF kappa B signaling, and indicate that the IFN gamma-induced IL-8 contributes to IFN gamma pro-tumorigenic effects in ovarian cancer cells.