Hypoxia-Nitric Oxide Axis and the Associated Damage Molecular Pattern in Cutaneous Melanoma

Hypoxia was intensively studied in cancer during the last few decades, being considered a characteristic of the tumor microenvironment. The aim of the study was to evaluate the capacity of tumor cells to adapt to the stress generated by limited oxygen tissue in cutaneous melanoma. We developed a cas...

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Bibliographic Details
Published inJournal of personalized medicine Vol. 12; no. 10; p. 1646
Main Authors Ene, Corina Daniela, Nicolae, Ilinca
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 04.10.2022
MDPI
Subjects
Angiogenesis
Cancer therapies
Homeostasis
Hypoxia
Hypoxia-inducible factor 1a
Hypoxia-inducible factors
Laboratories
Lipid peroxidation
Medical prognosis
Medical research
Melanoma
Metabolic disorders
Metabolism
Metabolites
Nitrates
Nitric oxide
Nitric-oxide synthase
Oxygen
Patients
Precision medicine
Proteins
Serum levels
Therapeutic targets
Tumor cells
Tumor microenvironment
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Summary:Hypoxia was intensively studied in cancer during the last few decades, being considered a characteristic of the tumor microenvironment. The aim of the study was to evaluate the capacity of tumor cells to adapt to the stress generated by limited oxygen tissue in cutaneous melanoma. We developed a case–control prospective study that included 52 patients with cutaneous melanoma and 35 healthy subjects. We focused on identifying and monitoring hypoxia, the dynamic of nitric oxide (NO) serum metabolites and posttranslational metabolic disorders induced by NO signaling according to the clinical, biological and tumoral characteristics of the melanoma patients. Our study showed high levels of hypoxia-inducible factor-1a (HIF-1a) and hypoxia-inducible factor-2a (HIF-2a) in the melanoma patients. Hypoxia-inducible factors (HIFs) control the capacity of tumor cells to adapt to low levels of oxygen. Hypoxia regulated the nitric oxide synthase (NOS) expression and activity. In the cutaneous melanoma patients, disorders in NO metabolism were detected. The serum levels of the NO metabolites were significantly higher in the melanoma patients. NO signaling influenced the tumor microenvironment by modulating tumoral proliferation and sustaining immune suppression. Maintaining NO homeostasis in the hypoxic tumoral microenvironment could be considered a future therapeutic target in cutaneous melanoma.
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ISSN:2075-4426
2075-4426
DOI:10.3390/jpm12101646