Figure 6: IL-33 mediates PDGF-BB-stimulated cancer metastasis through a TAM-dependent mechanism.

(a) Clodronate effectively inhibited Iba1⁺ macrophage infiltration (green) in IL-33-T241 tumours. Tumour cells were labelled with RFP (red). Arrowheads indicate TAMs. Quantification of Iba1⁺ macrophage in clodronate-treated and non-treated vector- and IL-33-T241 tumours (n=8 random fields per group). (b) Lung metastasis in clodronate-treated and non-treated vector- and IL-33-T241 tumour-bearing mice. Arrowheads indicate lung surface metastatic nodules. Dashed line marks the border between the RFP⁺ metastatic nodule and surrounding lung tissues. T, tumour. Quantification of percentage of animals with pulmonary metastasis on the surface of lungs (n=10–16 mice per group). (c) Detection of Iba1⁺ macrophages (red) and tumour cells (green) in vehicle- and soluble ST2-treated PDGF-BB-T241 tumours implanted in wt mice. Iba1⁺ macrophages (red) were also detected in PDGF-BB-T241 tumours implanted in St2^−/− mice. Vector-T241 tumour serves as a control. The detection of Iba1⁺ macrophages (red) and tumour cells (green) in PDGF-BB-LLC tumours implanted in wt and Il33^−/− mice. Vector-LLC tumour serves as a control. Arrowheads indicate Iba1⁺ macrophages. Quantification of Iba1⁺ macrophages (n=8 random fields per group). (d) Pulmonary metastasis in vehicle- and soluble ST2-treated PDGF-BB-T241 tumour-bearing mice. Pulmonary metastasis in PDGF-BB-LLC tumour-bearing wt and Il33^−/− mice. Metastases were detected by gross examination of lung surface, fluorescent detection for GFP⁺ signals and histological staining with H&E. Arrowheads indicate lung and liver surface metastases in tumour-bearing mice. Dashed lines encircle the borders between tumour nodules and surrounding tissues. T, tumour. Quantification of lung surface metastases in tumour-bearing mice (n=8–10 mice per group; mean±s.e.m., NS, not significant, Student’s t-test).