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Home / Equine Research Bank / Cells / Deregulation of Metalloproteinase Expression in Gray Horse M...
Cells2024; 13(11); doi: 10.3390/cells13110956

Deregulation of Metalloproteinase Expression in Gray Horse Melanoma Ex Vivo and In Vitro.

Abstract: The ability of human melanoma cells to switch from an epithelial to a mesenchymal phenotype contributes to the metastatic potential of disease. Metalloproteinases (MPs) are crucially involved in this process by promoting the detachment of tumor cells from the primary lesion and their migration to the vasculature. In gray horse melanoma, epithelial-mesenchymal transition (EMT) is poorly understood, prompting us to address MP expression in lesions versus intact skin by transcriptome analyses and the immunofluorescence staining (IF) of gray horse tumor tissue and primary melanoma cells. RNAseq revealed the deregulation of several MPs in gray horse melanoma and, notably, a 125-fold upregulation of matrix metalloproteinase 1 (MMP1) that was further confirmed by RT-qPCR from additional tumor material. The IF staining of melanoma tissue versus intact skin for MMP1 and tumor marker S100 revealed MMP1 expression in all lesions. The co-expression of S100 was observed at different extents, with some tumors scoring S100-negative. The IF staining of primary tumor cells explanted from the tumors for MMP1 showed that the metalloproteinase is uniformly expressed in the cytoplasm of 100% of tumor cells. Overall, the presented data point to MP expression being deregulated in gray horse melanoma, and suggest that MMP1 has an active role in gray horse melanoma by driving EMT-mediated tumor cell dissemination via the degradation of the extracellular matrix. Whilst S100 is considered a reliable tumor marker in human MM, gray horse melanomas do not seem to regularly express this protein.
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Publication Date: 2024-05-31 PubMed ID: 38891088PubMed Central: PMC11172212DOI: 10.3390/cells13110956Google 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 article discusses the role of certain enzymes, known as Metalloproteinases (MPs), in the transition and spread of melanoma – a form of skin cancer – in gray horses.

Study’s Purpose

  • The researchers aimed to study the expression of Metalloproteinases (MPs) in melanoma tumors of gray horses. MPs are a group of enzymes that contribute to the metastatic potential of diseases, such as melanoma, by detaching tumor cells from primary lesions and enabling their migration.
  • The focus was on the Epithelial-Mesenchymal Transition (EMT), a process responsible for the spread of cancer, which remains poorly understood in the context of gray horse melanoma.

Methodology

  • The researchers analyzed MP expression by conducting transcriptome analyses (which catalogues all the RNA transcripts produced in a cell) as well as immunofluorescence staining (which visualizes specific proteins in cells or tissue) of tumor tissue and primary melanoma cells.
  • A particularly marked finding from the study was a 125-fold increase in one particular MP, Matrix Metalloproteinase 1 (MMP1), as confirmed by RT-qPCR, which is a technique used to measure RNA levels.

Findings

  • The immuno-fluorescence staining of melanoma tissue versus intact skin for MMP1 showed MMP1 expression in all tumors.
  • Researchers also found that this MP was expressed in the cytoplasm of all the tumor cells analysed from these tumors. This may imply that MMP1 plays a vital role in driving the EMT-mediated tumor cell spread in gray horses through the degradation of the extracellular matrix – the structural network outside of cells.
  • While the S100 protein is often used as a reliable tumor marker in human Melanoma Maligna (MM), the study observed varying levels of its expression in gray horse melanomas. Some melanoma tumors did not express the S100 protein at all.

Conclusion

  • The findings indicate that MP expression shows deregulation in gray horse melanoma, suggesting specific enzymes might have an active role in the disease’s progression.
  • The irregular expression of the S100 protein in this melanoma suggests that it may not be as reliable a tumor marker in gray horse melanoma as in human MM.

Cite This Article

APA
Brodesser DM, Kummer S, Eichberger JA, Schlangen K, Corteggio A, Borzacchiello G, Bertram CA, Brandt S, Pratscher B. (2024). Deregulation of Metalloproteinase Expression in Gray Horse Melanoma Ex Vivo and In Vitro. Cells, 13(11). https://doi.org/10.3390/cells13110956

Publication

Cells
ISSN: 2073-4409
NlmUniqueID: 101600052
Country: Switzerland
Language: English
Volume: 13
Issue: 11

Researcher Affiliations

Brodesser, Daniela M
  • Research Group Oncology (RGO), Centre for Equine Health and Research, Department for Small Animals and Horses, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.
Kummer, Stefan
  • VetImaging, VetCore Facility, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.
Eichberger, Julia A
  • Research Group Oncology (RGO), Centre for Equine Health and Research, Department for Small Animals and Horses, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.
Schlangen, Karin
  • Section for Biosimulation and Bioinformatics, Centre for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna (MUV), Waehringer Guertel 18-20, 1090 Vienna, Austria.
Corteggio, Annunziata
  • Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Via Pietro Castellino 111, 80131 Naples, Italy.
Borzacchiello, Giuseppe
  • Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Corso Umberto I 40, 80138 Naples, Italy.
Bertram, Christof A
  • Institute of Pathology, Department of Pathobiology, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.
Brandt, Sabine
  • Research Group Oncology (RGO), Centre for Equine Health and Research, Department for Small Animals and Horses, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.
Pratscher, Barbara
  • Division of Small Animal Internal Medicine, Department for Small Animals and Horses, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.

MeSH Terms

  • Animals
  • Melanoma / pathology
  • Melanoma / enzymology
  • Melanoma / genetics
  • Melanoma / metabolism
  • Horses
  • Gene Expression Regulation, Neoplastic
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 1 / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Skin Neoplasms / pathology
  • Skin Neoplasms / enzymology
  • Skin Neoplasms / genetics
  • Skin Neoplasms / veterinary
  • Skin Neoplasms / metabolism
  • Cell Line, Tumor
  • Metalloproteases / metabolism
  • Metalloproteases / genetics
  • Humans

Grant Funding

  • 2012 / Vienna's Spanish Riding School

Conflict of Interest Statement

The authors declare no conflicts of interest. The funding organization had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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