Moreover, a marked reduction in vascular endothelial growth factor (VEGF) expression, CD31+ blood vessels, CD4+ Foxp3+ Treg cells and the expression of MMP-2, MMP-9, MMP-13 and C-X-C motif chemokine receptor 4 (CXCR4) in the tumour stroma were observed in the Smad3−/− tumour microenvironment (Supplementary Figs 5 and 6). Here, SMAD3 is linked to neoplasm.