Inhibition of MMP-1 expression by antisense RNA decreases invasiveness of human chondrosarcoma.
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.
Jiang
Xiaoling
X
Department of Orthopaedic Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Dutton
Charyl M
CM
Qi
Wen ning
Wn
Block
Joel A
JA
Brodt
Pnina
P
Durko
Margaret
M
Scully
Sean P
SP
D002465:Cell Movement / Q000235:genetics; D002813:Chondrosarcoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D017364:Collagenases / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects
D061965:Matrix Metalloproteinase Inhibitors; D016372:RNA, Antisense; D012333:RNA, Messenger; D017364:Collagenases; C417249:collagenase 1; D020781:Matrix Metalloproteinase 1