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Home / Equine Research Bank / Virology / Equine sarcoid fibroblasts over-express matrix metalloprotei...
Virology2009; 396(1); 143-151; doi: 10.1016/j.virol.2009.10.010

Equine sarcoid fibroblasts over-express matrix metalloproteinases and are invasive.

Abstract: 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.
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Publication Date: 2009-11-06 PubMed ID: 19896685DOI: 10.1016/j.virol.2009.10.010Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research examines how bovine papillomaviruses cause skin tumors in cattle and horses, known as sarcoids, and determines that over-expressed proteins called matrix metalloproteinases (MMPs) can cause these sarcoid fibroblasts to become invasive. The study also suggests potential treatment methods for these tumours.

Research Background

  • The study focuses on bovine papillomaviruses which are known to cause skin tumors, specifically termed sarcoids, in both cattle and equids.
  • The over-expression of specific matrix metalloproteinases (MMPs) like Collagenase (MMP-1) and Gelatinase (MMP-2, MMP-9) is often seen in such sarcoid fibroblasts and tumors.

Research Findings

  • The team extended their observations to several other MMPs and verified if these MMPs induce the invasion of sarcoid fibroblasts, leading to the spread of tumors.
  • It was observed that the over-expression of MMPs indeed led to sarcoid fibroblasts becoming invasive.
  • To valid this finding, an experiment was conducted using a 3D/matrigel invasion assay system where it was found that the inhibition of MMPs significantly reduced this invasion.

Significance of the E2 Protein

  • E2 siRNA treatment was applied to sarcoid fibroblasts which resulted in a reduction of the expression of viral genes and of MMP-2 and -9, dramatically reducing the invasion.
  • This highlighted the role of the E2 protein in inducing the over-expression of MMPs that contribute to the invasiveness of these sarcoid fibroblasts.
  • Inhibiting the E2 protein with siRNA leads to a halt of invasion, suggesting the E2 protein as a potential target for sarcoid treatment.

Research Implications

  • The study provides a better understanding of how papillomaviruses cause tumors and how they spread within a host.
  • It also presents the potential of using the inhibition of E2 proteins as a treatment method for sarcoids.
  • Further research on this subject of E2 proteins could potentially lead to effective treatments for these specific types of skin tumors caused by bovine papillomaviruses.

Cite This Article

APA
Yuan Z, Gobeil PA, Campo MS, Nasir L. (2009). Equine sarcoid fibroblasts over-express matrix metalloproteinases and are invasive. Virology, 396(1), 143-151. https://doi.org/10.1016/j.virol.2009.10.010

Publication

Virology
ISSN: 1096-0341
NlmUniqueID: 0110674
Country: United States
Language: English
Volume: 396
Issue: 1
Pages: 143-151

Researcher Affiliations

Yuan, ZhengQiang
  • Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, UK.
Gobeil, Philipe A M
    Campo, M Saveria
      Nasir, Lubna

        MeSH Terms

        • Animals
        • Bovine papillomavirus 1 / physiology
        • Cattle
        • Cell Line, Tumor
        • DNA-Binding Proteins / physiology
        • Fibroblasts / enzymology
        • Fibroblasts / physiology
        • Horse Diseases / enzymology
        • Horse Diseases / pathology
        • Horses
        • Matrix Metalloproteinase 1 / analysis
        • Matrix Metalloproteinase 1 / physiology
        • Matrix Metalloproteinase 9 / analysis
        • Matrix Metalloproteinase 9 / physiology
        • Matrix Metalloproteinases / analysis
        • Matrix Metalloproteinases / physiology
        • Neoplasm Invasiveness
        • Skin Neoplasms / enzymology
        • Skin Neoplasms / pathology
        • Skin Neoplasms / veterinary
        • Viral Proteins / physiology

        Grant Funding

        • Cancer Research UK

        Citations

        This article has been cited 10 times.
        1. Daraban Bocaneti F, Altamura G, Corteggio A, Tanase OI, Dascalu MA, Pasca SA, Hritcu O, Mares M, Borzacchiello G. Expression of collagenases (matrix metalloproteinase-1, -8, -13) and tissue inhibitor of metalloproteinase-3 (TIMP-3) in naturally occurring bovine cutaneous fibropapillomas.. Front Vet Sci 2022;9:1072672.
          doi: 10.3389/fvets.2022.1072672pubmed: 36713871google scholar: lookup
        2. Daraban Bocaneti F, Altamura G, Corteggio A, Tanase OI, Dascalu MA, Pasca SA, Hritcu O, Mares M, Borzacchiello G. Expression of matrix metalloproteinases (MMPs)-2/-7/-9/-14 and tissue inhibitors of MMPs (TIMPs)-1/-2 in bovine cutaneous fibropapillomas associated with BPV-2 infection.. Front Vet Sci 2022;9:1063580.
          doi: 10.3389/fvets.2022.1063580pubmed: 36518899google scholar: lookup
        3. Barton AK, Richter IG, Ahrens T, Merle R, Alalwani A, Lilge S, Purschke K, Barnewitz D, Gehlen H. MMP-9 Concentration in Peritoneal Fluid Is a Valuable Biomarker Associated with Endotoxemia in Equine Colic.. Mediators Inflamm 2021;2021:9501478.
          doi: 10.1155/2021/9501478pubmed: 33488296google scholar: lookup
        4. Podstawski P, Witarski W, Szmatoła T, Bugno-Poniewierska M, Ropka-Molik K. Mobility and Invasion Related Gene Expression Patterns in Equine Sarcoid.. Animals (Basel) 2020 May 19;10(5).
          doi: 10.3390/ani10050880pubmed: 32438542google scholar: lookup
        5. Ramsauer AS, Wachoski-Dark GL, Fraefel C, Tobler K, Brandt S, Knight CG, Favrot C, Grest P. Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions.. BMC Vet Res 2019 Oct 22;15(1):356.
          doi: 10.1186/s12917-019-2097-0pubmed: 31640696google scholar: lookup
        6. Deng H, Hillpot E, Mondal S, Khurana KK, Woodworth CD. HPV16-Immortalized Cells from Human Transformation Zone and Endocervix are More Dysplastic than Ectocervical Cells in Organotypic Culture.. Sci Rep 2018 Oct 18;8(1):15402.
          doi: 10.1038/s41598-018-33865-2pubmed: 30337615google scholar: lookup
        7. Martano M, Corteggio A, Restucci B, De Biase ME, Borzacchiello G, Maiolino P. Extracellular matrix remodeling in equine sarcoid: an immunohistochemical and molecular study.. BMC Vet Res 2016 Feb 2;12:24.
          doi: 10.1186/s12917-016-0648-1pubmed: 26838095google scholar: lookup
        8. Mosseri S, Hetzel U, Hahn S, Michaloupoulou E, Sallabank HC, Knottenbelt DC, Kipar A. Equine sarcoid: In situ demonstration of matrix metalloproteinase expression.. Vet J 2014 Nov;202(2):279-85.
          doi: 10.1016/j.tvjl.2014.07.026pubmed: 25439440google scholar: lookup
        9. Corteggio A, Altamura G, Roperto F, Borzacchiello G. Bovine papillomavirus E5 and E7 oncoproteins in naturally occurring tumors: are two better than one?. Infect Agent Cancer 2013 Jan 9;8(1):1.
          doi: 10.1186/1750-9378-8-1pubmed: 23302179google scholar: lookup
        10. Finlay M, Yuan Z, Morgan IM, Campo MS, Nasir L. Equine sarcoids: Bovine Papillomavirus type 1 transformed fibroblasts are sensitive to cisplatin and UVB induced apoptosis and show aberrant expression of p53.. Vet Res 2012 Dec 4;43(1):81.
          doi: 10.1186/1297-9716-43-81pubmed: 23210796google scholar: lookup
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