This domain is not involved in cell-ECM association but instead regulates the activity of metalloproteases such as ADAM17 (26, 37) and metalloprotease inhibitors such as TIMP-3 (59), both of which exert extensive control over ECM protein cleavage, activation of cell-membrane receptors, and release of soluble signals to the tumor microenvironment. This evidence concerns the gene ADAM17 and neoplasm.