Suppression of invasive behavior of melanoma cells by stable expression of anti-sense perlecan cDNA

Background: Heparan sulfate proteoglycans are one of the major componentsof extracellular matrix and are secreted at different levels by severalnormal and tumoral cells. Perlecan, the basement membrane proteoglycan, hasstructural domains involved in cell/matrix interactions and growth factorstorage. Metastatic melanoma cells show an increase in perlecan expressionas compared to low metastatic ones. We examined whether reduction ofperlecan expression could down-modulate the malignant phenotype in melanomaclones.Materials and methods: We transfected B16-F10 murine malignant melanomacells with a perlecan antisense cDNA construct and tested the in vitrobehavior of the selected clones.Results: The expression of antisense mRNA corresponded to a reduction ofperlecan synthesis. The clones with reduced perlecan synthesis showed adown-regulation of proliferation and invasion.Conclusions: These results further indicate the importance of perlecan asa regulator of growth factor activity affecting the biological properties ofmetastatic cells, and suggest the potential use of antisense perlecan DNA inanti-melanoma gene therapy approaches.