Fig. 7
TRIM59 stimulates macrophages to facilitate tumor growth and metastasis in vivo. a. Representative image of tumor growth in WT and TgTRIM59 mice subcutaneously inoculated with LLC cells (n = 5 per group). b. The growth curve of subcutaneous tumor in WT and TgTRIM59 mice. And comparison of tumor weight from two groups at the end of the experiment. c. LLC cells (5.0 × 106/100 μl of DMEM) were intravenously injected into WT and TgTRIM59 mice via the tail vein (n = 6 in each group). Mice were sacrificed for further observation on day 14. Representative images of lung metastasis in WT and TgTRIM59 mice. The total area of invasive lesions on the lung slice section represents the invasive tumor volume in the lungs. Immunoblotting assay of TRIM59 in TAMs from the lung metastases of WT or TgTRIM59 mice. Scale bars, 200 μm. d. Fluorescent multiplex immunohistochemistry (mIHC) staining of adjacent noncancerous tissues and LC tissues. Representative image of an LC case was shown with TRIM59 and IL-1β co-expression (DAPI, blue; TRIM59, red; IL-1β, green; CD68, yellow). Scale bars, 200 μm. e. multiplex immunohistochemistry analysis of TRIM59 and IL-1β protein levels in lung cancer samples on tissue microarrays. The expression of TRIM59 and IL-1β expression in TAMs were measured with mean fluorescence intensities (MFIs) (in arbitrary units, a.u.), respectively. The Pearson correlation between TRIM59 and IL-1β expression (n = 90; p < 0.01, r = 0.414). f. Chematic illustration of the crosstalk between macrophages and cancer cells in the tumor microenvironment. Our data indicate that exosomal TRIM59 stimulates macrophages NLRP3 inflammasome activation to release IL1-β, which, in turn, promotes LC cells proliferation and invasion. All data are shown as mean ± SEM. Student’s t-test was used to analyze the data. **p < 0.01