Patient-reported Outcomes from JAVELIN Bladder 100: Avelumab First-line Maintenance Plus Best Supportive Care Versus Best Supportive Care Alone for Advanced Urothelial Carcinoma

To determine whether substance P induces the expression of adhesion molecules ICAM-1 and VCAM-1 on vascular endothelial cells, we examined the effect of substance P, its carboxyl- and amino-terminal peptides, and neurokinin A on the expression of ICAM-1 and VCAM-1 on cultured human umbilical vein endothelial cells (HUVEC). Substance P and the carboxyl-terminal peptide SP(6–11), but not the amino-terminal peptide SP(1–9) or neurokinin A, increased ICAM-1 expression on HUVEC. In contrast, substance P did not significantly induce VCAM-1 expression on HUVEC. Furthermore, stimulation of HUVEC with substance P increased neutrophil transendothelial migration through an ICAM-1-dependent mechanism, as indicated by the inhibitory effect of anti-ICAM-1 antibody. These results indicate that substance P induces ICAM-1 expression on vascular endothelial cells and thereby enhances neutrophil transendothelial migration.