Inhibition of MMP-1 expression by antisense RNA decreases invasiveness of human chondrosarcoma

Abstract

We previously reported that an elevated level of matrix metalloproteinase-1 (MMP-1) gene expression in patients with chondrosarcoma has a strong statistical correlation with recurrence and in vitro invasion. In the present study, we used an antisense RNA strategy for MMP-1 inhibition to determine if this would affect the invasive characteristics of the cells. We transfected a human chondrosarcoma cell line with a retroviral plasmid expressing a 770 bp genomic fragment of the human MMP-1 gene in the sense or antisense orientation. The results show that cells transfected with the MMP-1 antisense fragment had a significant decrease in both MMP-1 protein and enzyme activity (p<0.05) as compared to cells transfected with an empty plasmid or the parental cells. Cells transfected with the MMP-1 antisense fragment demonstrated a significant decrease in their ability to invade the collagen I barrier (p<0.05). The gene expression for MMP-8 and MMP-13 were unaffected in cells transfected with the MMP-1 antisense fragment, MMP-1 sense fragment, or empty plasmid. These results support the hypothesis that MMP-1 facilitates tumor cell egress from chondrosarcoma tissue and demonstrate the potential of MMP-1 as a promising target for a novel biologic therapy in chondrosarcoma.