SUPPRESSION OF INVASIVE BEHAVIOR OF MELANOMA-CELLS BY STABLE EXPRESSION OF ANTISENSE PERLECAN CDNA

Background: Heparan sulfate proteoglycans are one of the major compone nts of extracellular matrix and are secreted at different levels by se veral normal and tumoral cells. Perlecan, the basement membrane proteo glycan, has structural domains involved in cell/matrix interactions an d growth factor storage. Metastatic melanoma cells show an increase in perlecan expression as compared to low metastatic ones. We examined w hether reduction of perlecan expression could down-modulate the malign ant phenotype in melanoma clones. Materials and Methods. We transfecte d B16-F10 murine malignant melanoma cells with a perlecan antisense cD NA 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 show ed 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 metasta tic cells, and suggest the potential use of antisense perlecan DNA in anti-melanoma gene therapy approaches.