PMID- 37047096 OWN - NLM STAT- MEDLINE DCOM- 20230415 LR - 20231213 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 7 DP - 2023 Mar 24 TI - CA-IX-Expressing Small Extracellular Vesicles (sEVs) Are Released by Melanoma Cells under Hypoxia and in the Blood of Advanced Melanoma Patients. LID - 10.3390/ijms24076122 [doi] LID - 6122 AB - 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. FAU - Venturella, Marta AU - Venturella M AD - Cellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy. FAU - Falsini, Alessandro AU - Falsini A AUID- ORCID: 0009-0005-2636-6443 AD - Cellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy. FAU - Coppola, Federica AU - Coppola F AUID- ORCID: 0000-0002-7201-5741 AD - Cellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy. FAU - Giuntini, Gaia AU - Giuntini G AUID- ORCID: 0000-0001-6643-1354 AD - Cellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy. FAU - Carraro, Fabio AU - Carraro F AUID- ORCID: 0000-0003-0771-042X AD - Cellular and Molecular Physiology Unit, Department of Medical Biotechnologies, University of Siena, Via A. Moro 2, 53100 Siena, Italy. FAU - Zocco, Davide AU - Zocco D AD - Lonza Siena, Strada del Petriccio e Belriguardo 35, 53100 Siena, Italy. FAU - Chiesi, Antonio AU - Chiesi A AD - Exosomics SpA, Strada del Petriccio e Belriguardo 35, 53100 Siena, Italy. FAU - Naldini, Antonella AU - Naldini A AUID- ORCID: 0000-0002-9600-2486 AD - Cellular and Molecular Physiology Unit, Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy. LA - eng PT - Journal Article DEP - 20230324 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antigens, Neoplasm) RN - 0 (Biomarkers, Tumor) RN - EC 4.2.1.1 (Carbonic Anhydrase IX) RN - EC 4.2.1.1 (Carbonic Anhydrases) RN - EC 4.2.1.1 (CA9 protein, human) SB - IM MH - Humans MH - Antigens, Neoplasm/metabolism MH - Biomarkers, Tumor/metabolism MH - Carbonic Anhydrase IX/genetics MH - *Carbonic Anhydrases/metabolism MH - Hypoxia MH - *Melanoma/genetics MH - *Skin Neoplasms MH - Tumor Microenvironment MH - Melanoma, Cutaneous Malignant PMC - PMC10094632 OTO - NOTNLM OT - HIF-1 OT - biomarker discovery OT - carbonic anhydrase IX OT - hypoxia OT - liquid biopsy OT - melanoma OT - sEVs COIS- The authors declare no conflict of interest. EDAT- 2023/04/14 06:00 MHDA- 2023/04/14 06:41 PMCR- 2023/03/24 CRDT- 2023/04/13 01:10 PHST- 2023/01/27 00:00 [received] PHST- 2023/03/17 00:00 [revised] PHST- 2023/03/22 00:00 [accepted] PHST- 2023/04/14 06:41 [medline] PHST- 2023/04/13 01:10 [entrez] PHST- 2023/04/14 06:00 [pubmed] PHST- 2023/03/24 00:00 [pmc-release] AID - ijms24076122 [pii] AID - ijms-24-06122 [pii] AID - 10.3390/ijms24076122 [doi] PST - epublish SO - Int J Mol Sci. 2023 Mar 24;24(7):6122. doi: 10.3390/ijms24076122.