Switching Roles─Exploring Concentration-Dependent Agonistic versus Antagonistic Behavior of Integrin Ligands.

ABSTRACT: Identification of integrins as cancer targets has stimulated the development of specific inhibitory ligands. However, following cilengitide's unexpected clinical failure by promoting angiogenesis at low concentrations, pure ligand antagonism was soon scrutinized. We evaluated αvβ3, αvβ6, or α5β1 ligands for concentration-dependent functional switches in respective integrin subtype-overexpressing cancer cells. Cilengitide (L2) or L1 provoked minor transient changes in (p)-FAK and (p)-p44/42^(erk-1/2) predominantly at low concentrations and antagonized cell migration at high concentrations, while agonistically accelerating it at low concentrations. L5 (α5β1) showed bell-shaped FAK activation at both concentrations, blocking cell migration at high concentrations only in α5β1+ OV-MZ-

SUBMITTER: Ludwig BS 

PROVIDER: S-EPMC11874007 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature