Lumican Inhibits SNAIL-Induced Melanoma Cell Migration Specifically by Blocking MMP-14 Activity

Lumican, a small leucine rich proteoglycan, inhibits MMP-14 activity and melanoma cell migration in vitro and in vivo. Snail triggers epithelial-mesenchymal transitions endowing epithelial cells with migratory and invasive properties during tumor progression. The aim of this work was to investigate lumican effects on MMP-14 activity and migration of Snail overexpressing B16F1 (Snail-B16F1) melanoma cells and HT-29 colon adenocarcinoma cells. Lumican inhibits the Snail induced MMP-14 activity in B16F1 but not in HT-29 cells. In Snail-B16F1 cells, lumican inhibits migration, growth, and melanoma primary tumor development. A lumican-based strategy targeting Snail-induced MMP-14 activity might be useful for melanoma treatment.

Highlights

Snail stimulates MMP-14 activity in Snail overexpressing B16F1 melanoma cells but not in HT29 cells; Lumican inhibits the Snail-induced MMP-14 activity in Snail-B16F1 cells; Lumican inhibits the migration and growth of Snail-B16F1 cells in vitro; Lumican inhibits melanoma primary tumor growth of Snail-B16F1 cells in vivo.