Recombinant thrombomodulin domain 1 (TMD1, equivalent to lectin-like domain) binds Lewis Y antigen (LeY)–containing proteins such as epidermal growth factor receptor (EGFR) via which it neutralizes the angiogenic action of EGF and thereby suppresses tumor angiogenesis and growth. TMD1 was previously shown to bind LeY-containing lipopolysaccharide (LPS) and attenuate LPS-induced inflammation and tissue damage. The dotted lime depicts possible release of the lectin-like domain into circulating blood as a component of soluble thrombomodulin (sTM). Soluble lectin-like domain may act in a manner similar to TMD1 and may serve as a sensor of LeY for control of LeY-induced pathophysiologic processes.