In addition, the secretory proteases MMPs and urokinase-type plasminogen activator (uPA) that cleave key ECM proteins, including collagen, elastin, and fibronectin, thereby facilitating immune cell infiltration, driving EMT through PDGF, HGF, and IL-1, and enhancing migration and metastasis, effects reinforced by tumor-associated macrophage-derived factors in a pro-tumorigenic feedback loop. The gene discussed is PLAU; the disease is neoplasm.