Integrin-binding peptide in solution inhibits or enhances endothelial cell migration, predictably from cell adhesion

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Abstract
We have examined the effects of an integrin-binding competitor, echistatin, in solution on adhesion and migration of rat microvessel endothelial cells on fibronectinin vitro. A biphasic dependence of cell motility on fibronectin surface density was observed, with a peak random motility coefficient of about 8 × 10−9 cm2/sec occurring below 0.3 μg/cm2 fibronectin. In the presence of echistatin at 0.5 μM, the peak random motility coefficient was similar but occurred at the significantly greater fibronectin surface density of 1.2 μg/cm2. Hence, the same concentration of this soluble integrin-binding competitor inhibited migration on low fibronectin densities but enhanced migration on high fibronectin densities. At the same time, echistatin decreased adhesiveness on all fibronectin surface densities. When motility was correlated explicitly with adhesiveness, a single biphasic relationship was obtained for both absence and presence of echistatin with peak motility occuring in both cases at identical adhesiveness. Both the inhibiting and enhancing effects of the soluble integrin-binding competitor on motility are predictable from its effect on adhesion, consistent with the theoretical models of Lauffenburger (15) and DiMillaet al. (3).