Deregulation of Metalloproteinase Expression in Gray Horse Melanoma Ex Vivo and In Vitro
Daniela M. Brodesser,
Stefan Kummer,
Julia A. Eichberger,
Karin Schlangen,
Annunziata Corteggio,
Giuseppe Borzacchiello,
Christof A. Bertram,
Sabine Brandt,
Barbara Pratscher
Affiliations
Daniela M. Brodesser
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
Stefan Kummer
VetImaging, VetCore Facility, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria
Julia A. Eichberger
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
Karin Schlangen
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
Annunziata Corteggio
Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Via Pietro Castellino 111, 80131 Naples, Italy
Giuseppe Borzacchiello
Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Corso Umberto I 40, 80138 Naples, Italy
Christof A. Bertram
Institute of Pathology, Department of Pathobiology, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria
Sabine Brandt
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
Barbara Pratscher
Division of Small Animal Internal Medicine, Department for Small Animals and Horses, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria
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.
