CA-IX-Expressing Small Extracellular Vesicles (sEVs) Are Released by Melanoma Cells under Hypoxia and in the Blood of Advanced Melanoma Patients

• Published in: International journal of molecular sciences Vol. 24; no. 7; p. 6122
• Main Authors: Venturella, Marta, Falsini, Alessandro, Coppola, Federica, Giuntini, Gaia, Carraro, Fabio, Zocco, Davide, Chiesi, Antonio, Naldini, Antonella
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.03.2023; MDPI
• Subjects: Antibodies; Antigens, Neoplasm - metabolism; biomarker discovery; Biomarkers; Biomarkers, Tumor - metabolism; Biopsy; Cancer therapies; Carbonic anhydrase; carbonic anhydrase IX; Carbonic Anhydrase IX - genetics; Carbonic Anhydrases - metabolism; Cell growth; Enzyme-linked immunosorbent assay; Extracellular vesicles; Genes; HIF-1; Humans; Hypoxia; Hypoxia-inducible factor 1; Medical prognosis; Melanoma; Melanoma - genetics; Melanoma, Cutaneous Malignant; Metastasis; Mitochondrial DNA; mRNA; Protein expression; Proteins; Scientific equipment and supplies industry; sEVs; Skin cancer; Skin Neoplasms; Tumor Microenvironment; Tumors; Vesicles; United States; United Kingdom; California; HIF-1; hypoxia; carbonic anhydrase IX; melanoma; sEVs; biomarker discovery; liquid biopsy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24076122

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.