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

Abstract

Background: Heparan sulfate proteoglycans are one of the major components of extracellular matrix and are secreted at different levels by several normal and tumoral cells. Perlecan, the basement membrane proteoglycan, has structural domains involved in cell/matrix interactions and growth factor storage. Metastatic melanoma cells show an increase in perlecan expression as compared to low metastatic ones. We examined whether reduction of perlecan expression could down-modulate the malignant phenotype in melanoma clones. Materials and methods: We transfered B16-F10 murine malignant melanoma cells with a perlecan antisense cDNA construct and tested the in vitro behavior of the selected clones. Results: The expression of antisense mRNA corresponded to a reduction of perlecan synthesis. The clones with reduced perlecan synthesis showed a down-regulation of proliferation and invasion. Conclusions: These results further indicate the importance of perlecan as a regulator of growth factor activity affecting the biological properties of metastatic cells, and suggest the potential use of antisense perlecan DNA in anti-melanoma gene therapy approaches.