Taken together, these results i) provide a quantitative explanation of limiting factors in using decoy antibodies against growth-factor ligands, particularly relevant to high affinity ligands such as HB-EGF; ii) demonstrate ADAM12 as a relevant sheddase of HB-EGF in endometriosis; and iii) present a novel, specific ADAM12 inhibitor to reduce HB-EGF shedding and resulting cell migration behavior. Here, ADAM12 is linked to endometriosis.