Abstract:
The aim of this study is to investigate IDO expression and metastasis ability of lung carcinoma cells after co-culturing with mast cells. Mast cells were obtained from C57BL/6 mice (aged 4—6 weeks), and a cellular phenotype analysis was performed by flow cytometry. IDO expression in lung carcinoma cells was detected by real-time PCR and western blotting. Transwell migration and invasion assays were used to assess the metastasis capacity of lung carcinoma cells. Moreover, the effects of culturing lung carcinoma cells with mast cells on the STAT3 and TIMP/MMP signaling pathways were determined by western blotting. Afterwards, metastatic-associated gene expression data were obtained from Gene Expression Omnibus database with 2 metastatic samples and 2 healthy samples. We subsequently analyzed differentially expressed genes (DEGs) in metastatic colonization using R software. IDO expression in lung carcinoma cells was attenuated after co-culturing with mast cells. The migration and invasion abilities of lung carcinoma cells in the co-culture system were decreased. The identified DEGs including 1 368 mRNAs were dysregulated in metastatic nodes. TIMP1 was down-regulated in metastatic nodes. The mechanisms by which mast cells restrain the metastasis behavior of lung carcinoma cell as well as the STAT3 signaling pathway, and limit MMP2/MMP9 expression by promoting TIMP1 expression. In conclusion, Mast cells restrain the expression of IDO in lung carcinoma cells by inhibiting STAT3 phosphorylation. The migration and invasion ability of lung carcinoma cells were restricted by the facilitated TIMP1 expression. Our study demonstrates a novel mechanism by which mast cells limit the lung carcinoma angiogenesis.