Equine sarcoid fibroblasts over-express matrix metalloproteinases and are invasive.
Papillomaviruses are DNA viruses that cause tumours of the skin in humans and animals. The natural host of bovine papillomavirus is cattle, but also equids, resulting in tumours termed sarcoids. Matrix metalloproteinase 1 (MMP-1) expression is up-regulated in sarcoid fibroblasts and tumours. We extended our observation to other MMPs and determined whether MMPs induced invasion of sarcoid fibroblasts. Collagenase (MMP-1) and Gelatinase (MMP-2, MMP-9) were over-expressed in sarcoid fibroblasts and tumours. The fibroblasts were invasive in a 3D/matrigel invasion assay system. Inhibition of MMP by GM6001 significantly reduced invasion. E2 siRNA treatment of sarcoid fibroblasts decreased the expression of the viral genes and of MMP-2 and -9, leading to a dramatic reduction of invasion. This demonstrates that BPV-1 induces over-expression of MMPs contributing to invasiveness of sarcoid fibroblasts. Inhibition of E2 by siRNA leads to abrogation of invasion suggesting that E2 is a good target for sarcoid treatment.
Yuan
ZhengQiang
Z
Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, UK.
Gobeil
Philipe A M
PA
Campo
M Saveria
MS
Nasir
Lubna
L
D000818:Animals; D052688:Bovine papillomavirus 1 / Q000502:physiology; D002417:Cattle; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000502:physiology; D005347:Fibroblasts / Q000201:enzymology* / Q000502:physiology; D006734:Horse Diseases / Q000201:enzymology / Q000473:pathology*; D006736:Horses; D020781:Matrix Metalloproteinase 1 / Q000032:analysis / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000032:analysis / Q000502:physiology*; D009361:Neoplasm Invasiveness; D012878:Skin Neoplasms / Q000201:enzymology / Q000473:pathology / Q000662:veterinary*; D014764:Viral Proteins / Q000502:physiology
D004268:DNA-Binding Proteins; C051550:E2 protein, Bovine papillomavirus; D014764:Viral Proteins; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1