CA-IX-Expressing Small Extracellular Vesicles (sEVs) Are Released by Melanoma Cells under Hypoxia and in the Blood of Advanced Melanoma Patients
Cutaneous melanoma is a highly aggressive skin cancer, with poor prognosis. The tumor microenvironment is characterized by areas of hypoxia. Carbonic anhydrase IX (CA-IX) is a marker of tumor hypoxia and its expression is regulated by hypoxia-inducible factor-1 (HIF-1). CA-IX has been found to be hi...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/7/6122 |
| _version_ | 1797607858045452288 |
|---|---|
| author | Marta Venturella Alessandro Falsini Federica Coppola Gaia Giuntini Fabio Carraro Davide Zocco Antonio Chiesi Antonella Naldini |
| author_facet | Marta Venturella Alessandro Falsini Federica Coppola Gaia Giuntini Fabio Carraro Davide Zocco Antonio Chiesi Antonella Naldini |
| author_sort | Marta Venturella |
| collection | DOAJ |
| description | Cutaneous melanoma is a highly aggressive skin cancer, with poor prognosis. The tumor microenvironment is characterized by areas of hypoxia. Carbonic anhydrase IX (CA-IX) is a marker of tumor hypoxia and its expression is regulated by hypoxia-inducible factor-1 (HIF-1). CA-IX has been found to be highly expressed in invasive melanomas. In this study, we investigated the effects of hypoxia on the release of small extracellular vesicles (sEVs) in two melanoma in vitro models. We demonstrated that melanoma cells release sEVs under both normoxic and hypoxic conditions, but only hypoxia-induced sEVs express CA-IX mRNA and protein. Moreover, we optimized an ELISA assay to provide evidence for CA-IX protein expression on the membranes of the sEVs. These CA-IX-positive sEVs may be exploited as potential biomarkers for liquid biopsy. |
| first_indexed | 2024-03-11T05:35:30Z |
| format | Article |
| id | doaj.art-1062f65fb62e4eac800082269eb0fda0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:35:30Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1062f65fb62e4eac800082269eb0fda02023-11-17T16:46:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247612210.3390/ijms24076122CA-IX-Expressing Small Extracellular Vesicles (sEVs) Are Released by Melanoma Cells under Hypoxia and in the Blood of Advanced Melanoma PatientsMarta Venturella0Alessandro Falsini1Federica Coppola2Gaia Giuntini3Fabio Carraro4Davide Zocco5Antonio Chiesi6Antonella Naldini7Cellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, ItalyCellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, ItalyCellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, ItalyCellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, ItalyCellular and Molecular Physiology Unit, Department of Medical Biotechnologies, University of Siena, Via A. Moro 2, 53100 Siena, ItalyLonza Siena, Strada del Petriccio e Belriguardo 35, 53100 Siena, ItalyExosomics SpA, Strada del Petriccio e Belriguardo 35, 53100 Siena, ItalyCellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, ItalyCutaneous melanoma is a highly aggressive skin cancer, with poor prognosis. The tumor microenvironment is characterized by areas of hypoxia. Carbonic anhydrase IX (CA-IX) is a marker of tumor hypoxia and its expression is regulated by hypoxia-inducible factor-1 (HIF-1). CA-IX has been found to be highly expressed in invasive melanomas. In this study, we investigated the effects of hypoxia on the release of small extracellular vesicles (sEVs) in two melanoma in vitro models. We demonstrated that melanoma cells release sEVs under both normoxic and hypoxic conditions, but only hypoxia-induced sEVs express CA-IX mRNA and protein. Moreover, we optimized an ELISA assay to provide evidence for CA-IX protein expression on the membranes of the sEVs. These CA-IX-positive sEVs may be exploited as potential biomarkers for liquid biopsy.https://www.mdpi.com/1422-0067/24/7/6122melanomasEVshypoxiaHIF-1carbonic anhydrase IXbiomarker discovery |
| spellingShingle | Marta Venturella Alessandro Falsini Federica Coppola Gaia Giuntini Fabio Carraro Davide Zocco Antonio Chiesi Antonella Naldini CA-IX-Expressing Small Extracellular Vesicles (sEVs) Are Released by Melanoma Cells under Hypoxia and in the Blood of Advanced Melanoma Patients International Journal of Molecular Sciences melanoma sEVs hypoxia HIF-1 carbonic anhydrase IX biomarker discovery |
| title | CA-IX-Expressing Small Extracellular Vesicles (sEVs) Are Released by Melanoma Cells under Hypoxia and in the Blood of Advanced Melanoma Patients |
| title_full | CA-IX-Expressing Small Extracellular Vesicles (sEVs) Are Released by Melanoma Cells under Hypoxia and in the Blood of Advanced Melanoma Patients |
| title_fullStr | CA-IX-Expressing Small Extracellular Vesicles (sEVs) Are Released by Melanoma Cells under Hypoxia and in the Blood of Advanced Melanoma Patients |
| title_full_unstemmed | CA-IX-Expressing Small Extracellular Vesicles (sEVs) Are Released by Melanoma Cells under Hypoxia and in the Blood of Advanced Melanoma Patients |
| title_short | CA-IX-Expressing Small Extracellular Vesicles (sEVs) Are Released by Melanoma Cells under Hypoxia and in the Blood of Advanced Melanoma Patients |
| title_sort | ca ix expressing small extracellular vesicles sevs are released by melanoma cells under hypoxia and in the blood of advanced melanoma patients |
| topic | melanoma sEVs hypoxia HIF-1 carbonic anhydrase IX biomarker discovery |
| url | https://www.mdpi.com/1422-0067/24/7/6122 |
| work_keys_str_mv | AT martaventurella caixexpressingsmallextracellularvesiclessevsarereleasedbymelanomacellsunderhypoxiaandinthebloodofadvancedmelanomapatients AT alessandrofalsini caixexpressingsmallextracellularvesiclessevsarereleasedbymelanomacellsunderhypoxiaandinthebloodofadvancedmelanomapatients AT federicacoppola caixexpressingsmallextracellularvesiclessevsarereleasedbymelanomacellsunderhypoxiaandinthebloodofadvancedmelanomapatients AT gaiagiuntini caixexpressingsmallextracellularvesiclessevsarereleasedbymelanomacellsunderhypoxiaandinthebloodofadvancedmelanomapatients AT fabiocarraro caixexpressingsmallextracellularvesiclessevsarereleasedbymelanomacellsunderhypoxiaandinthebloodofadvancedmelanomapatients AT davidezocco caixexpressingsmallextracellularvesiclessevsarereleasedbymelanomacellsunderhypoxiaandinthebloodofadvancedmelanomapatients AT antoniochiesi caixexpressingsmallextracellularvesiclessevsarereleasedbymelanomacellsunderhypoxiaandinthebloodofadvancedmelanomapatients AT antonellanaldini caixexpressingsmallextracellularvesiclessevsarereleasedbymelanomacellsunderhypoxiaandinthebloodofadvancedmelanomapatients |