Abstract
Lung cancer is one of the most common human cancers and is the leading cause of cancer-related mortality. Previous studies have suggested that IL-22 might promote the survival of human lung cancer cells. However, the source of IL-22 and the regulatory mechanism of lung cancer cell proliferation remain unclear. In this study, we found that the expression of IL-22 was upregulated in non-small-cell lung cancer (NSCLC) tumor specimens, as revealed by RT-qPCR analysis. Furthermore, IL-22 was profoundly elevated in cell cultures of primary cancer-associated fibroblasts (CAFs) compared to the levels in cell cultures of normal fibroblasts. Moreover, treatment with the supernatant of CAF cell cultures significantly increased the proliferation, migration and invasion of A549 and H1650 cells but reduced apoptosis via the activation of PI3K-Akt-mTOR signaling, and the application of an anti-IL-22 antibody can partially block the effects induced by the CAF cell culture supernatant. Finally, we also identified a panel of critical genes with differential expression between A549 cells treated with and without IL-22. In summary, our results demonstrate a novel regulatory function of IL-22 secreted by CAFs in NSCLC and provide a potential therapeutic target for treating lung cancer.