PLAU and neoplasm: Because these two PA variants (together termed Intermolecular Complementation version 2, or IC2-PA; Table S1, Supplementary Material) require MMPs and uPA, respectively, for activation, the action of this intermolecular complementation system relies on the presence of two distinct tumor-associated proteases, thereby achieving high tumor specificity (16, 17), and minimizing the side effects that have limited previous therapy (21).