Fig. 1

High levels of exosomal ADAM17 in the serum correlate with lower VE-cadherin levels at the tumor invasive front in patients with metastatic colorectal cancer (CRC). (a) Proteomic analysis of serum-derived exosomal proteins differentially expressed between non-metastatic (primary), liver metastatic, lung metastatic, and both liver and lung metastatic patients with CRC. The resultant heatmap shows the differentially expressed exosomal proteins based on quantitative mass spectrometry values; all protein analysis was performed in technical triplicate (* false discovery rate < 0.05 determined via ANOVA). Hierarchical clustering was performed on protein expression levels (n = 3) using the Spearman’s rank correlation coefficient to identify similarities. (b) Relative CirExo-ADAM17, TRPC5, ANXA2, and CD63 protein levels in non-metastatic (primary), liver metastatic, lung metastatic, and both liver and lung metastatic patients with CRC (n = 6). (c) Representative immunohistochemistry staining for VE-cadherin, p120, and EMT (E-cadherin and vimentin) in the invasive front of tumors from patients with CRC (scale bar = 100 μm). (d) Correlation analysis of cirExo-ADAM17 protein levels and immunostaining intensity of VE-cadherin, p120, E-cadherin, and vimentin at the invasive front. (e) Linear regression between the expression of CirExo-ADAM17 protein, immunostaining intensity of VE-cadherin at the invasive front, and total CTC count, respectively. Data are expressed as mean ± standard deviation. **P < 0.01, compared with the primary group; ##P < 0.01, compared with the liver metastasis and lung metastasis groups