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Fig. 6 | Journal of Translational Medicine

Fig. 6

From: Loss of endothelial EMCN drives tumor lung metastasis through the premetastatic niche

Fig. 6

Notch inhibition upregulated EMCN expression in HUVECs, and combination therapy with DAPT and anti-TGF-β inhibited lung metastasis. A The association of TGF-β and EMCN in all specimens was analyzed using online datasets (https://hiplot.com.cn/advance/correlation-analyzer). B The efficiency of NICD knockdown in HUVECs was measured by Western blotting, and NICD downregulation increased EMCN protein levels in HUVECs. C HUVECs were cocultured with B16-F10, ACC-LM and LLC cell conditioned medium for 48 h. NICD and EMCN expression levels in HUVECs were detected by Western blotting. D Schematic diagram showing the experimental procedure of subcutaneous implantation of LLC tumor cells, DAPT or anti-TGF-β injection, tumor resection and lung analysis (upper). Representative images of tumors harvested from WT mice with vehicle or DAPT after 21 days of LLC tumor implantation (below). E Growth curves of LLC tumors in WT mice treated with vehicle, DAPT alone, anti-TGF-β antibody alone, or a combination of anti-TGF-β antibody with DAPT. Tumors were measured by a caliper every other day. n = 5 mice per group. **p < 0.01, two-way ANOVA. F H&E sections of mouse lungs 3 weeks after subcutaneous tumor resection treated with vehicle, DAPT alone, anti-TGF-β antibody alone, or the combination of anti-TGF-β antibody with DAPT (left). Histological quantification of the area of lung invasion (right). *p < 0.05, **p < 0.01, ***p < 0.001

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