Besides the enhanced NK cell immunity, we also observed that upregulation of angiogenesis markers (for example, VEGF and CD31+ vessels) and cancer invasive and metastatic proteins (for example, MMP-2, MMP-9, MMP-13 and CXCR4) were largely inhibited in the tumour microenvironment of Smad3−/− mice and in Smad3+/+ mice treated with SIS3. This evidence concerns the gene MMP2 and neoplasm.