Human lung adenocarcinoma CD47 is upregulated by interferon-γ and promotes tumor metastasis

Tumor cells can evade attack by phagocytes by upregulating the self-marker CD47. The mechanisms underlying tumor CD47 upregulation, however, remain unclear. Here, we report that human lung adenocarcinoma CD47 is upregulated by interferon-gamma (IFN-gamma), the level in the tumor microenvironment of which is markedly increased after tumor metastasis and chemotherapy. The IFN- gamma receptor is expressed in various human lung adenocarcinoma tissues regardless of the CD47 protein expression, and lung adenocarcinoma CD47 expression is significantly enhanced following tumor metastasis or chemotherapy treatment. In line with this, CD47 expression in various lung cancer cells is markedly increased by IFN-g treatment. Mechanistically, IFN- gamma promotes CD47 expression by activating interferon regulatory factor-1 (IRF-1), which binds to an IRF1-binding domain within the CD47 promoter region and increases CD47 transcription. Functionally, IFN-gamma-enhanced CD47 expression facilitates human lung cancer cell invasion both in vitro and in vivo, whereas IFN-gamma-induced CD47 upregulation and cancer metastasis are blocked by mutating the IRF-1binding site within the CD47 promoter. Our results reveal IFN gamma-enhanced CD47 expression as a novel mechanism promoting human lung adenocarcinoma progression.