Equine sarcoid: In situ demonstration of matrix metalloproteinase expression.
Abstract: Sarcoids are the most prevalent equine skin tumours and remain a therapeutic challenge due to their differing clinical morphology, local aggressive behaviour, and high recurrence following surgical treatment. In vitro, sarcoid derived fibroblasts are invasive and express matrix metalloproteinase (MMP) -1, -2 and -9. It was hypothesised that the MMPs produced by neoplastic cells play a role in both their local invasiveness and interaction with the overlying epidermis (picket fence formation). The objective of this morphological study was to investigate the local behaviour and in situ MMP expression pattern in sarcoids of different clinical types. A total of 43 surgically excised sarcoids were examined by histology, immunohistology for the expression of MMP-1, -2 and -9, and transmission electron microscopy. Regardless of the clinical type, sarcoids showed local invasion of the dermis and damage to the basement membrane in areas of interaction with the epidermis. This was associated with MMP-1 expression in both neoplastic cells and epidermis. The results suggest a link between MMP-1 expression and the local aggressiveness of sarcoids regardless of the clinical type.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication Date: 2014-08-28 PubMed ID: 25439440PubMed Central: PMC7128672DOI: 10.1016/j.tvjl.2014.07.026Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
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 study examines the role of certain proteins (MMP -1, -2 and -9) in the aggressive behavior of equine sarcoids, a prevalent skin tumor in horses, and how they may contribute to their high recurrence rate after surgical treatment.
Study Goals and Methods
- The goal of the study was to understand the local behavior and expression patterns of matrix metalloproteinase (MMP), specific proteins known to be associated with the tissue remodeling of cancerous cells, in various clinical types of sarcoids. The researchers hypothesize that these proteins are partly responsible for the tumors’ aggressive behavior and high risk of recurrence after surgery.
- To gather data, a total of 43 surgically removed sarcoids were examined using three different techniques: histology, immunohistology, and transmission electron microscopy. Histology allowed researchers to study the structure of the tumors, while immunohistology was used to inspect the expression of MMP-1, -2, and -9 and electron microscopy gave detailed images at a cellular level.
Findings
- The researchers found that, no matter the clinical type of sarcoid, the tumors demonstrated behavior of local invasion into the dermis, or the second layer of skin, and damages to the basement membrane, a crucial boundary between the outermost layer of skin and the underlying tissue.
- Moreover, these invasive behaviors were found to be associated with the expression of MMP-1, both in the tumor cells and the epidermis, the outermost layer of skin. This connection suggests that MMP-1 may play a crucial role in the local aggressive behavior and high recurrence of equine sarcoids.
Conclusions
- This study brings us one step closer to understanding the pathophysiology of equine sarcoids, the most common skin tumor in horses. The strong link between the tumors’ aggressive behaviors and the expression of MMP-1, not only in the tumor cells but also in the epidermis, suggests the significant role this protein plays in the local invasion and high recurrence of the disease.
- This insight could lead to targeted therapeutic approaches in managing equine sarcoids, potentially reducing the likelihood of recurrence and improving outcomes following surgeries. Further research into MMP-1’s role could also provide insights into other similar skin tumors in both animals and humans.
Cite This Article
APA
Mosseri S, Hetzel U, Hahn S, Michaloupoulou E, Sallabank HC, Knottenbelt DC, Kipar A.
(2014).
Equine sarcoid: In situ demonstration of matrix metalloproteinase expression.
Vet J, 202(2), 279-285.
https://doi.org/10.1016/j.tvjl.2014.07.026 Publication
Researcher Affiliations
- Philip Leverhulme Equine Hospital, School of Veterinary Science, University of Liverpool, Leahurst, Neston, Wirral CH64 7TE, UK; Three Counties Equine Hospital, Ripple, Tewkesbury GL20 6HE, UK.
- Veterinary Pathology, Faculty of Veterinary Medicine, University of Helsinki, Agnes Sjöbergin katu 2, 00014 Helsinki, Finland.
- Veterinary Pathology, Faculty of Veterinary Medicine, University of Helsinki, Agnes Sjöbergin katu 2, 00014 Helsinki, Finland.
- Veterinary Epidemiology and Public Health, School of Veterinary Science, University of Liverpool, Leahurst, Neston, Wirral CH64 7TE, UK.
- Veterinary Pathology, School of Veterinary Science, University of Liverpool, Liverpool Science Park IC2, 146 Brownlow Hill, Liverpool L3 5RF, UK; Department of Infection Biology, University of Liverpool, Liverpool Science Park IC2, 146 Brownlow Hill, Liverpool L3 5RF, UK.
- Philip Leverhulme Equine Hospital, School of Veterinary Science, University of Liverpool, Leahurst, Neston, Wirral CH64 7TE, UK.
- Veterinary Pathology, Faculty of Veterinary Medicine, University of Helsinki, Agnes Sjöbergin katu 2, 00014 Helsinki, Finland; Veterinary Pathology, School of Veterinary Science, University of Liverpool, Liverpool Science Park IC2, 146 Brownlow Hill, Liverpool L3 5RF, UK; Department of Infection Biology, University of Liverpool, Liverpool Science Park IC2, 146 Brownlow Hill, Liverpool L3 5RF, UK. Electronic address: anja.kipar@uzh.ch.
MeSH Terms
- Animals
- Female
- Gene Expression Regulation, Neoplastic
- Histology
- Horse Diseases / genetics
- Horses
- Male
- Matrix Metalloproteinase 1 / genetics
- Matrix Metalloproteinase 1 / metabolism
- Matrix Metalloproteinase 2 / genetics
- Matrix Metalloproteinase 2 / metabolism
- Matrix Metalloproteinase 9 / genetics
- Matrix Metalloproteinase 9 / metabolism
- Microscopy, Electron, Transmission / veterinary
- Sarcoidosis / genetics
- Sarcoidosis / veterinary
- Skin Neoplasms / genetics
- Skin Neoplasms / veterinary
References
This article includes 33 references
- Bogaert L, Martens A, Kast WM, Van Marck E, De Cock H. Bovine papillomavirus DNA can be detected in keratinocytes of equine sarcoid tumors.. Vet Microbiol 2010 Dec 15;146(3-4):269-75.
- Brandt S, Tober R, Corteggio A, Burger S, Sabitzer S, Walter I, Kainzbauer C, Steinborn R, Nasir L, Borzacchiello G. BPV-1 infection is not confined to the dermis but also involves the epidermis of equine sarcoids.. Vet Microbiol 2011 May 12;150(1-2):35-40.
- Breitkreutz D, Koxholt I, Thiemann K, Nischt R. Skin basement membrane: the foundation of epidermal integrity--BM functions and diverse roles of bridging molecules nidogen and perlecan.. Biomed Res Int 2013;2013:179784.
- Chen Y, Chen Y, Huang L, Yu J. Evaluation of heparanase and matrix metalloproteinase-9 in patients with cutaneous malignant melanoma.. J Dermatol 2012 Apr;39(4):339-43.
- Fields GB. Interstitial collagen catabolism.. J Biol Chem 2013 Mar 29;288(13):8785-93.
- Hartl B, Hainisch EK, Shafti-Keramat S, Kirnbauer R, Corteggio A, Borzacchiello G, Tober R, Kainzbauer C, Pratscher B, Brandt S. Inoculation of young horses with bovine papillomavirus type 1 virions leads to early infection of PBMCs prior to pseudo-sarcoid formation.. J Gen Virol 2011 Oct;92(Pt 10):2437-2445.
- Kähäri VM, Saarialho-Kere U. Matrix metalloproteinases in skin.. Exp Dermatol 1997 Oct;6(5):199-213.
- Kipar A, Baumgärtner W, Burkhardt E. Round cell sarcomas of possible myelomonocytic origin localized at the lip of aged dogs.. Zentralbl Veterinarmed A 1995 May;42(3):185-200.
- Kipar A, May H, Menger S, Weber M, Leukert W, Reinacher M. Morphologic features and development of granulomatous vasculitis in feline infectious peritonitis.. Vet Pathol 2005 May;42(3):321-30.
- Knottenbelt DC. A suggested clinical classification for the equine sarcoid.. Clinical Techniques in Equine Practice 2005;4:278–295.
- Knottenbelt DC, Kelly DF. The diagnosis and treatment of periorbital sarcoid in the horse: 445 cases from 1974 to 1999.. Vet Ophthalmol 2000;3(2-3):169-191.
- Krengel S, Alexander M, Brinckmann J, Tronnier M. MMP-2, TIMP-2 and MT1-MMP are differentially expressed in lesional skin of melanocytic nevi and their expression is modulated by UVB-light.. J Cutan Pathol 2002 Aug;29(7):390-6.
- Martens A, De Moor A, Demeulemeester J, Ducatelle R. Histopathological characteristics of five clinical types of equine sarcoid.. Res Vet Sci 2000 Dec;69(3):295-300.
- Martens A, De Moor A, Ducatelle R. PCR detection of bovine papilloma virus DNA in superficial swabs and scrapings from equine sarcoids.. Vet J 2001 May;161(3):280-6.
- Martens A, De Moor A, Vlaminck L, Pille F, Steenhaut M. Evaluation of excision, cryosurgery and local BCG vaccination for the treatment of equine sarcoids.. Vet Rec 2001 Dec 1;149(22):665-9.
- Martens A, De Moor A, Demeulemeester J, Peelman L. Polymerase chain reaction analysis of the surgical margins of equine sarcoids for bovine papilloma virus DNA.. Vet Surg 2001 Sep-Oct;30(5):460-7.
- Marti E, Lazary S, Antczak DF, Gerber H. Report of the first international workshop on equine sarcoid.. Equine Vet J 1993 Sep;25(5):397-407.
- McMillan JR, Akiyama M, Shimizu H. Epidermal basement membrane zone components: ultrastructural distribution and molecular interactions.. J Dermatol Sci 2003 May;31(3):169-77.
- Miragliotta V, Lefebvre-Lavoie J, Lussier JG, Theoret CL. Equine ANXA2 and MMP1 expression analyses in an experimental model of normal and pathological wound repair.. J Dermatol Sci 2008 Aug;51(2):103-12.
- Pascoe RRR, Knottenbelt DC. Neoplastic conditions.. 1999; pp. 27–31.
- Scott DW, Miller WH Jr. Neoplastic and non-neoplastic tumours.. 2003; pp. 719–731.
- Shapiro SD. Matrix metalloproteinase degradation of extracellular matrix: biological consequences.. Curr Opin Cell Biol 1998 Oct;10(5):602-8.
- Tarwid JN, Fretz PB, Clark EG. Equine sarcoids: A study with emphasis on pathologic diagnosis.. The Compendium of Continuing Education 1985;7:293–300.
- Torrontegui BO, Reid SWJ. Clinical and pathological epidemiology of the equine sarcoid in a referral population.. Equine Veterinary Education 1994;6:85–88.
- Väisänen A, Tuominen H, Kallioinen M, Turpeenniemi-Hujanen T. Matrix metalloproteinase-2 (72 kD type IV collagenase) expression occurs in the early stage of human melanocytic tumour progression and may have prognostic value.. J Pathol 1996 Nov;180(3):283-9.
- Villone D, Fritsch A, Koch M, Bruckner-Tuderman L, Hansen U, Bruckner P. Supramolecular interactions in the dermo-epidermal junction zone: anchoring fibril-collagen VII tightly binds to banded collagen fibrils.. J Biol Chem 2008 Sep 5;283(36):24506-13.
- Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry.. Circ Res 2003 May 2;92(8):827-39.
- Westermarck J, Kähäri VM. Regulation of matrix metalloproteinase expression in tumor invasion.. FASEB J 1999 May;13(8):781-92.
- Williams IF, Heaton A, McCullagh KG. Connective tissue composition of the equine sarcoid.. Equine Vet J 1982 Oct;14(4):305-10.
- Yuan ZQ, Nicolson L, Marchetti B, Gault EA, Campo MS, Nasir L. Transcriptional changes induced by bovine papillomavirus type 1 in equine fibroblasts.. J Virol 2008 Jul;82(13):6481-91.
- Yuan ZQ, Gault EA, Gobeil P, Nixon C, Campo MS, Nasir L. Establishment and characterization of equine fibroblast cell lines transformed in vivo and in vitro by BPV-1: model systems for equine sarcoids.. Virology 2008 Apr 10;373(2):352-61.
- Yuan ZQ, Bennett L, Campo MS, Nasir L. Bovine papillomavirus type 1 E2 and E7 proteins down-regulate Toll Like Receptor 4 (TLR4) expression in equine fibroblasts.. Virus Res 2010 Apr;149(1):124-7.
- Yuan Z, Gobeil PA, Campo MS, Nasir L. Equine sarcoid fibroblasts over-express matrix metalloproteinases and are invasive.. Virology 2010 Jan 5;396(1):143-51.
Citations
This article has been cited 6 times.- 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.
- 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.
- 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.
- 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.
- Araldi RP, Assaf SMR, Carvalho RF, Carvalho MACR, Souza JM, Magnelli RF, Módolo DG, Roperto FP, Stocco RC, Beçak W. Papillomaviruses: a systematic review.. Genet Mol Biol 2017 Jan-Mar;40(1):1-21.
- 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.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists