Lumican, a
small leucine-rich proteoglycan of the extracellular matrix, presents potent anti-
tumor properties. Previous works from our group showed that
lumican inhibited
melanoma cell migration and
tumor growth in vitro and in vivo.
Melanoma cells adhered to
lumican, resulting in a remodeling of their actin cytoskeleton and preventing their migration. In addition, we identified a sequence of 17
amino acids within the
lumican core
protein, named
lumcorin, which was able to inhibit cell chemotaxis and reproduce anti-migratory effect of
lumican in vitro. The aim of the present study was to characterize the anti-
tumor mechanism of action of
lumcorin.
Lumcorin significantly decreased the growth in monolayer and in soft
agar of two
melanoma cell lines - mice B16F1 and human SK-MEL-28 cells - in comparison to controls. Addition of
lumcorin to serum free medium significantly inhibited spontaneous motility of these two
melanoma cell lines. To characterize the mechanisms involved in the inhibition of cell migration by
lumcorin, the status of the phosphorylation/dephosphorylation of
proteins was examined. Inhibition of
focal adhesion kinase phosphorylation was observed in presence of
lumcorin. Since
cancer cells have been shown to migrate and to invade by mechanisms that involve
matrix metalloproteinases (
MMPs), the expression and activity of
MMPs were analyzed.
Lumcorin induced an accumulation of an intermediate form of MMP-14 (~59kDa), and inhibited MMP-14 activity. Additionally, we identified a short, 10
amino acids peptide within
lumcorin sequence, which was able to reproduce its anti-
tumor effect on
melanoma cells. This
peptide may have potential pharmacological applications.