DPPA inhibits melanoma by targeting angiogenesis through activating autocrine IFN-γ-CXCL9/10/11-CXCR3 axis in vascular endothelial cells

Antiangiogenic therapy has been considered an effective therapeutic approach for malignant melanoma (MM). The use of bevacizumab, an antiangiogenic agent for targeting VEGF, has been associated with a potentially high rate of side effects in the treatment of different types of tumors. Therefore, exploration of innovative antiangiogenic therapeutic agents may be useful for the treatment of MM. Dipalmitoylphosphatidic acid (DPPA), a biologically active phosphatidic acid, performs various biological functions in different cancers. Nevertheless, whether DPPA affects tumor development in MM has not been fully elucidated. In this study, we demonstrated that DPPA suppresses tumor growth and metastasis by significantly inhibiting tumor angiogenesis, but not cell proliferation and invasion of MM. DPPA inhibits tumor neovascularization might through regulating interferon γ (IFN-γ)-related signaling, which can further activate CXCL9/10/11-chemokine receptor 3 (CXCR3) signaling. Our findings suggest that DPPA has the potential to serve as an effective antiangiogenic agent for the treatment of MM.