Stimulation of invasion of endothelial cells is blocked by SSTN, a peptide that inhibits syndecan-1–mediated activation of integrins. (A) Active SSTN peptide inhibits invasion of endothelial cells. The Matrigel invasion chamber assay was carried out using conditioned medium from HPSE-high or HPSE-low cells with addition of 1μM active SSTN_92-119, or inactive (control) SSTN_94-119 peptide_. *P < .05 vs HPSE-low. **P < .05 vs HPSE-high in the presence of SSTN_94-119. (B) Medium from HPSE-high cells was depleted of syndecan-1 (which also depletes VEGF). Addition of VEGF (which was added to all wells) and syndecan-1 to the medium restored the invasive phenotype, but this was blocked by addition of active SSTN. Addition of heparin (rather than syndecan-1) at a concentration similar to that of heparan sulfate present in the exogenous syndecan-1 (∼ 1 μg/mL) did not restore the highly invasive phenotype, whereas addition of 10 μg/mL heparin enhanced invasion as well exogenous syndecan-1. SSTN peptide failed to block cell invasion in the presence of the high (10 μg/mL) level of heparin.