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

Venturella, Marta; Falsini, Alessandro; Coppola, Federica; Giuntini, Gaia; Carraro, Fabio; Zocco, Davide; Chiesi, Antonio; Naldini, Antonella

doi:10.3390/ijms24076122

Cited by 5 publications

(2 citation statements)

References 62 publications

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“…On the contrary, CA-IX overexpression is associated with a variety of solid cancers including melanomas ( Chafe et al, 2019 ; Peppicelli et al, 2020 ). CA-IX is induced by HIF-1α and has been found to be highly expressed in invasive melanomas with only hypoxia-induced exosomes expressing CA-IX ( Venturella et al, 2023 ). In addition, CA-IX-expressing exosomes released from hypoxic renal cell carcinoma cells promote angiogenesis and migration of HUVEC, suggesting the involvement of this enzyme in cancer progression ( Horie et al, 2017 ).…”

Section: Role Of Exosomes In Angiogenesis Associated With Hypoxiamentioning

confidence: 99%

Targeting hypoxia signaling pathways in angiogenesis

Monaci,

Coppola,

Filippi

et al. 2024

Front. Physiol.

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Oxygen (O2) supply is constantly maintained by the vascular network for a proper tissue oxygenation. Hypoxia is the result of an increased O2 demand and/or decreased supply and is common in both physiological conditions and human diseases. Angiogenesis is one of the adaptive responses to hypoxia and is mainly regulated by the hypoxia-inducible factors, HIFs. These heterodimeric transcription factors are composed of one of three O2-dependent α subunits (HIF-1, HIF-2, and HIF-3) and a constitutively expressed O2-insensitive subunit (HIF-1β). Among them HIF-1α is the most characterized and its activity is tightly controlled. Under hypoxia, its intracellular accumulation triggers the transcription of several genes, involved in cell survival/proliferation, autophagy, apoptosis, cell metabolism, and angiogenesis. HIF pathway is also modulated by specific microRNAs (miRNAs), thus resulting in the variation of several cellular responses, including alteration of the angiogenic process. The pro-angiogenic activity of HIF-1α is not restricted to endothelial cells, as it also affects the behavior of other cell types, including tumor and inflammatory/immune cells. In this context, exosomes play a crucial role in cell-cell communication by transferring bio-active cargos such as mRNAs, miRNAs, and proteins (e.g., VEGFA mRNA, miR210, HIF-1α). This minireview will provide a synopsis of the multiple factors able to modulate hypoxia-induced angiogenesis especially in the tumor microenvironment context. Targeting hypoxia signaling pathways by up-to-date approaches may be relevant in the design of therapeutic strategies in those pathologies where angiogenesis is dysregulated.

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Section: Role Of Exosomes In Angiogenesis Associated With Hypoxiamentioning

confidence: 99%

Targeting hypoxia signaling pathways in angiogenesis

Monaci,

Coppola,

Filippi

et al. 2024

Front. Physiol.

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“…The transcription factor HIF-1 is a key regulator of carbonic anhydrase IX (CAIX) and phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) expression [14,15]. PFKFB4 and CAIX expression is upregulated during hypoxia in melanoma-derived cancer cells [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-Induced Changes in L-Cysteine Metabolism and Antioxidative Processes in Melanoma Cells

Rydz,

Wróbel,

Janik

et al. 2023

Biomolecules

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This study was performed on human primary (WM115) and metastatic (WM266-4) melanoma cell lines developed from the same individual. The expression of proteins involved in L-cysteine metabolism (sulfurtransferases, and cystathionine β-synthase) and antioxidative processes (thioredoxin, thioredoxin reductase-1, glutathione peroxidase, superoxide dismutase 1) as well as the level of sufane sulfur, and cell proliferation under hypoxic conditions were investigated. Hypoxia in WM115 and WM266-4 cells was confirmed by induced expression of carbonic anhydrase IX and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 by the RT-PCR and Western blot methods. It was shown that, under hypoxic conditions the inhibition of WM115 and WM266-4 melanoma cell proliferation was associated with decreased expression of thioredoxin reductase-1 and cystathionine β-synthase. These two enzymes may be important therapeutic targets in the treatment of melanoma. Interestingly, it was also found that in normoxia the expression and activity of 3-mercaptopyruvate sulfurtransferase in metastatic WM266-4 melanoma cells was significantly higher than in primary melanoma WM115 cells.

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