Ergolide mediates anti-cancer effects on metastatic uveal melanoma cells and modulates their cellular and extracellular vesicle proteomes
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Sundaramurthi, Husvinee1
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Tonelotto, Valentina2
- Wynne, Kieran3
- O'Connell, Fiona4
- O'Reilly, Eve5
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Costa-Garcia, Marcel6
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Kovácsházi, Csenger7
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Kittel, Agnes8
- Marcone, Simone4
- Blanco, Alfonso9
- Pallinger, Eva10
- Hambalkó, Szabolcs7
- Piulats Rodriguez, Jose Maria6
- Ferdinandy, Péter7
- O'Sullivan, Jacintha4
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Matallanas, David1
- Jensen, Lasse D.11
- Giricz, Zoltán7
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Kennedy, Breandán N.5
- 1. UCD School of Medicine, University College Dublin, Dublin, Leinster, Ireland
- 2. Xenopat S.L., Business Bioincubator, Bellvitge Health Science Campus, Barcelona, 08907 L'Hospitalet de Llobregat, Spain
- 3. Systems Biology Ireland, University College Dublin, Dublin, Leinster, Ireland
- 4. Department of Surgery, Trinity Translational Medicine Institute, Trinity St. James's Cancer Institute, St. James's Hospital, Trinity College Dublin, Dublin, Ireland
- 5. UCD School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Leinster, Ireland
- 6. Medical Oncology Department, Catalan Institute of Cancer (ICO), IDIBELL-OncoBell, Barcelona, Spain
- 7. Pharmahungary Group, Szeged, Hungary
- 8. Institute of Experimental Medicine, Budapest, Hungary
- 9. UCD Conway Institute, University College Dublin, Dublin, Leinster, Ireland
- 10. Department of Genetics and Immunobiology, Semmelweis University, Budapest, Hungary
- 11. BioReperia AB, Linköping, Sweden
Description
The most common form of adult eye cancer is uveal melanoma (UM). Once UM cancer cells spread to organs in the rest of the body, metastatic UM (MUM), there is a poor prognosis for patients with only one approved drug treatment. Hence, it is vital to better understand the cellular and extracellular proteins that regulate UM pathology in order to uncover biomarkers of disease and therapeutic targets. In this original study, we demonstrate a compound called ergolide is capable of severely reducing the metabolic activity and growth of UM cancer cells, grown as isolated monolayers. Ergolide was also able to reduce the growth of human MUM cells growing as tumors in transplanted zebrafish larvae. We identify that ergolide alters specific proteins found in the human UM cells. These proteins once analyzed in detail offer opportunities to understand how new treatment strategies can be developed for UM.
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