Extracellular matrix remodeling in equine sarcoid: an immunohistochemical and molecular study.
Abstract: Equine sarcoids are locally invasive, fibroblastic benign skin tumors. Bovine papillomavirus type-1 (BPV-1) and/or Bovine papillomavirus type-2 (BPV-2) are believed to be the causative agent of sarcoids, although the mechanisms by which the virus induce the tumor are still poorly understood. We hypothesized that in genetically predisposed equines latent BPV infection may be reactivated by immunosoppression and/or mechanical injury leading to a form of pathologic wound which may transform into a sarcoid. In this study, we investigated in 25 equine sarcoids and in five normal skin samples the histological features and evaluated the immunohistochemical and molecular expression of type I and type III Collagen, vimentin (VIM), alfa Smooth Muscle Actin (α-SMA), Matrix Metalloproteinase (MMPs) -2, 9, 14 and tissue inhibitor of metalloproteinase 2 (TIMP-2). Results: In 64% of investigated sarcoids, type I collagen staining was stronger than that of type III collagen. In 80% of sarcoids, SFs were strongly positive for vimentin and negative for α-SMA; the remaining sarcoid samples (20%) showed 70-80% of SFs labeled for vim and approximately 20-30% labeled for α-SMA. Moreover, all sarcoid specimen showed a variable staining pattern (weak to moderate) for MMP-9 and MMP-14, and a moderate to strong staining for MMP-2 and TIMP-2. Biochemical analysis confirmed immunohistochemical results and showed in sarcoids, for the first time, the cleaved form of MMP9, the 35 KDa active species for MMP-9. Conclusions: This study revealed that in equine sarcoids exhibit an altered turnover of the Extracellular Matrix (ECM) deposition and degradation, as result of an altered expression of MMPs and TIMPs. Therefore, these observations seem to confirm that the basic mechanism for growth of equine sarcoids could be a neoplastic transformation during wound healing.
Publication Date: 2016-02-02 PubMed ID: 26838095PubMed Central: PMC4736642DOI: 10.1186/s12917-016-0648-1Google Scholar: Lookup
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Summary
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The research explores the role of viruses and altered extracellular matrix turnover in causing equine sarcoids, a type of benign skin tumor in horses. The researchers proposed that sarcoids might result from a transformation during wound healing, examining the expression of collagens, vimentin, alpha Smooth Muscle Actin, Matrix Metalloproteinase, and Tissue Inhibitor of Metalloproteinase in 25 sarcoids and five normal skin samples.
Introduction and Hypothesis
- The study begins with an exploration of equine sarcoids, fibroblastic benign skin tumors found in horses. Although the main cause for these tumors is believed to be Bovine papillomavirus type-1 (BPV-1) and/or type-2 (BPV-2), the exact mechanisms are not entirely understood.
- The researchers hypothesized that these papillomaviruses might induce tumors in genetically predisposed horses, which could be reactivated by immunosuppression or mechanical injuries.
- This hypothesis revolved around the concept that wounds might transform into sarcoids due to a pathological or abnormal healing process.
Research Method and Results
- The research team examined 25 equine sarcoids and five normal skin samples, assessing the molecular expression of several proteins including type I and III Collagen, vimentin (VIM), alpha Smooth Muscle Actin (α-SMA), Matrix Metalloproteinase (MMPs) -2, 9, 14, and tissue inhibitor of metalloproteinase 2 (TIMP-2).
- Results showed 64% of sarcoids had strong staining for type I collagen than type III, while 80% evidenced significant vimentin positivity and negligible α-SMA expression. The remaining 20% had 70-80% vimentin label and approximately 20-30% α-SMA label.
- Furthermore, all sarcoid samples demonstrated variable staining for MMP-9 and MMP-14, and moderate to strong staining for MMP-2 and TIMP-2. Biochemical analysis revealed the cleaved form of MMP9, the 35 KDa active species for MMP-9.
Conclusions
- Findings indicated that equine sarcoids have a disrupted turnover of the Extracellular Matrix (ECM) due to altered expression of MMPs and TIMPs.
- The researchers inferred that this disrupted ECM turnover is a likely reason for the growth of equine sarcoids, affirming their hypothesis that a pathological transformation during the process of wound healing leads to the production of these skin tumors.
Cite This Article
APA
Martano M, Corteggio A, Restucci B, De Biase ME, Borzacchiello G, Maiolino P.
(2016).
Extracellular matrix remodeling in equine sarcoid: an immunohistochemical and molecular study.
BMC Vet Res, 12, 24.
https://doi.org/10.1186/s12917-016-0648-1 Publication
Researcher Affiliations
- Department of Veterinary Medicine and Animal Productions, Naples University "Federico II", Via F. Delpino 1, 80137, Naples, Italy. manuela.martano@unina.it.
- Present Address: Institute of Protein Biochemistry (IBP) National Research Council (CNR), Via Pietro Castellino 111, 80131, Naples, Italy. a.corteggio@ibp.cnr.it.
- Department of Veterinary Medicine and Animal Productions, Naples University "Federico II", Via F. Delpino 1, 80137, Naples, Italy. restucci@unina.it.
- Department of Veterinary Medicine and Animal Productions, Naples University "Federico II", Via F. Delpino 1, 80137, Naples, Italy. mariu12@hotmail.it.
- Department of Veterinary Medicine and Animal Productions, Naples University "Federico II", Via F. Delpino 1, 80137, Naples, Italy. giuseppe.borzacchiello@unina.it.
- Department of Veterinary Medicine and Animal Productions, Naples University "Federico II", Via F. Delpino 1, 80137, Naples, Italy. maiolino@unina.it.
MeSH Terms
- Animals
- Extracellular Matrix / metabolism
- Extracellular Matrix / pathology
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horses
- Matrix Metalloproteinase Inhibitors / metabolism
- Matrix Metalloproteinases / metabolism
- Skin Neoplasms / metabolism
- Skin Neoplasms / pathology
- Skin Neoplasms / veterinary
- Tissue Inhibitor of Metalloproteinase-2 / metabolism
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