The upregulation of genes encoding matrix associated factors including proteases and cell adhesion molecules such as ADAM12, NTN3, LRRC15, CDH17, PCDH19, VTN highlighted the relevance of the tumor microenvironment and cell–cell and cell–matrix interaction for progression to metastatic disease (Fig. 4a). This evidence concerns the gene LRRC15 and metastatic neoplasm.