Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation
Extracellular vesicles (EVs) carry molecules derived from donor cells and are able to alter the properties of recipient cells. They are important players during the genesis and progression of tumors. Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is associated with a...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/10/2923 |
| _version_ | 1797551326193778688 |
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| author | Thupten Tsering Alexander Laskaris Mohamed Abdouh Prisca Bustamante Sabrina Parent Eva Jin Sarah Tadhg Ferrier Goffredo Arena Julia V. Burnier |
| author_facet | Thupten Tsering Alexander Laskaris Mohamed Abdouh Prisca Bustamante Sabrina Parent Eva Jin Sarah Tadhg Ferrier Goffredo Arena Julia V. Burnier |
| author_sort | Thupten Tsering |
| collection | DOAJ |
| description | Extracellular vesicles (EVs) carry molecules derived from donor cells and are able to alter the properties of recipient cells. They are important players during the genesis and progression of tumors. Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is associated with a high rate of metastasis, primarily to the liver. However, the mechanisms underlying this process are poorly understood. In the present study, we analyzed the oncogenic potential of UM-derived EVs and their protein signature. We isolated and characterized EVs from five UM cell lines and from normal choroidal melanocytes (NCMs). BRCA1-deficient fibroblasts (Fibro-BKO) were exposed to the EVs and analyzed for their growth in vitro and their reprograming potential in vivo following inoculation into NOD-SCID mice. Mass spectrometry of proteins from UM-EVs and NCM-EVs was performed to determine a protein signature that could elucidate potential key players in UM progression. In-depth analyses showed the presence of exosomal markers, and proteins involved in cell-cell and focal adhesion, endocytosis, and PI3K-Akt signaling pathway. Notably, we observed high expression levels of HSP90, HSP70 and integrin V in UM-EVs. Our data bring new evidence on the involvement of UM-EVs in cancer progression and metastasis. |
| first_indexed | 2024-03-10T15:43:05Z |
| format | Article |
| id | doaj.art-0a750a2a72304c9b97b53f00678109ee |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T15:43:05Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0a750a2a72304c9b97b53f00678109ee2023-11-20T16:38:47ZengMDPI AGCancers2072-66942020-10-011210292310.3390/cancers12102923Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche PreparationThupten Tsering0Alexander Laskaris1Mohamed Abdouh2Prisca Bustamante3Sabrina Parent4Eva Jin5Sarah Tadhg Ferrier6Goffredo Arena7Julia V. Burnier8Cancer Research Program, Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, CanadaCancer Research Program, Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, CanadaCancer Research Program, Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, CanadaCancer Research Program, Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, CanadaCancer Research Program, Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, CanadaCancer Research Program, Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, CanadaCancer Research Program, Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, CanadaCancer Research Program, Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, CanadaCancer Research Program, Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, CanadaExtracellular vesicles (EVs) carry molecules derived from donor cells and are able to alter the properties of recipient cells. They are important players during the genesis and progression of tumors. Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is associated with a high rate of metastasis, primarily to the liver. However, the mechanisms underlying this process are poorly understood. In the present study, we analyzed the oncogenic potential of UM-derived EVs and their protein signature. We isolated and characterized EVs from five UM cell lines and from normal choroidal melanocytes (NCMs). BRCA1-deficient fibroblasts (Fibro-BKO) were exposed to the EVs and analyzed for their growth in vitro and their reprograming potential in vivo following inoculation into NOD-SCID mice. Mass spectrometry of proteins from UM-EVs and NCM-EVs was performed to determine a protein signature that could elucidate potential key players in UM progression. In-depth analyses showed the presence of exosomal markers, and proteins involved in cell-cell and focal adhesion, endocytosis, and PI3K-Akt signaling pathway. Notably, we observed high expression levels of HSP90, HSP70 and integrin V in UM-EVs. Our data bring new evidence on the involvement of UM-EVs in cancer progression and metastasis.https://www.mdpi.com/2072-6694/12/10/2923Uveal melanomaextracellular vesiclesliver metastasisliquid biopsymass spectrometry |
| spellingShingle | Thupten Tsering Alexander Laskaris Mohamed Abdouh Prisca Bustamante Sabrina Parent Eva Jin Sarah Tadhg Ferrier Goffredo Arena Julia V. Burnier Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation Cancers Uveal melanoma extracellular vesicles liver metastasis liquid biopsy mass spectrometry |
| title | Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation |
| title_full | Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation |
| title_fullStr | Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation |
| title_full_unstemmed | Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation |
| title_short | Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation |
| title_sort | uveal melanoma derived extracellular vesicles display transforming potential and carry protein cargo involved in metastatic niche preparation |
| topic | Uveal melanoma extracellular vesicles liver metastasis liquid biopsy mass spectrometry |
| url | https://www.mdpi.com/2072-6694/12/10/2923 |
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