ArticleInternational journal of cancer2012
The role of melanoma tumor-derived nitric oxide in the tumor inflammatory microenvironment: its impact on the chemokine expression profile, including suppression of CXCL10.
Article in International journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Intratumoral interferon-gamma increases chemokine production but fails to increase T cell infiltration of human melanoma metastases.Cancer immunology, immunotherapy : CII · 2016Trial
- Melanin as a Redox Hub: Linking Energy Flow to Genome Stability and Immune Control.Antioxidants & redox signaling · 2026Review
- Predicting anti-PD-1 immune checkpoint blockade response in melanoma patients with spatially aware machine learning models.NPJ precision oncology · 2026Article
- Gas-mediated reinforcement of cancer therapies: emerging strategies and future perspectives.Chemical science · 2025Review
- Reciprocal Modulation of Tumour and Immune Cell Motility: Uncovering Dynamic Interplays and Therapeutic Approaches.Cancers · 2025Review
- Natural killer cells: the immune frontline against circulating tumor cells.Journal of experimental & clinical cancer research : CR · 2025Review
- Enhancing Transcutaneous Drug Delivery: Advanced Perspectives on Skin Models.JID innovations : skin science from molecules to population health · 2025Review
- Stigmasterol Exerts an Anti-Melanoma Property through Down-Regulation of Reactive Oxygen Species and Programmed Cell Death Ligand 1 in Melanoma Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Gasotransmitters in the tumor microenvironment: Impacts on cancer chemotherapy (Review).Molecular medicine reports · 2022Review
- Oxidative stress in melanogenesis and melanoma development.Contemporary oncology (Poznan, Poland) · 2022Review
- Omega-3- and Resveratrol-Loaded Lipid Nanosystems for Potential Use as Topical Formulations in Autoimmune, Inflammatory, and Cancerous Skin Diseases.Pharmaceutics · 2021Article
- Identification of CXCL10-Relevant Tumor Microenvironment Characterization and Clinical Outcome in Ovarian Cancer.Frontiers in genetics · 2021Article
- Article
- Impact of l-Arginine Metabolism on Immune Response and Anticancer Immunotherapy.Frontiers in oncology · 2018Review
- The role of nitric oxide in melanoma.Biochimica et biophysica acta. Reviews on cancer · 2017Review
- Nitric Oxide: The Forgotten Child of Tumor Metabolism.Trends in cancer · 2017Review
- Article
- Inflammatory Marker Testing Identifies CD74 Expression in Melanoma Tumor Cells, and Its Expression Associates with Favorable Survival for Stage III Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Molecular mechanisms of flavonoids in melanin synthesis and the potential for the prevention and treatment of melanoma.Molecular nutrition & food research · 2016Review
- Immunology Comes Full Circle in Melanoma While Specific Immunity Is Unleashed to Eliminate Metastatic Disease, Inflammatory Products of Innate Immunity Promote Resistance.Critical reviews in oncogenesis · 2016Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Melanoma appears to be heterogeneous in terms of its molecular biology, etiology and epidemiology. We previously reported that the expression of inducible nitric-oxide synthase (iNOS) in melanoma tumor cells is strongly correlated with poor patient survival. Therefore, we hypothesized that nitric oxide (NO) produced by iNOS promotes the melanoma inflammatory tumor microenvironment associated with poor outcome. To understand the role of NO and iNOS in the melanoma inflammatory tumor microenvironment, polymerase chain reaction arrays of inflammatory and autoimmunity genes were performed on a series of stage III melanoma lymph node metastasis samples to compare the gene expression profiles of iNOS-expressing and nonexpressing tumor samples. The results indicate that expression of CXC chemokine ligand 10 (CXCL10) was inversely correlated with iNOS expression, and the high CXCL10-expressing cases had more favorable prognoses than the low CXCL10-expressing cases. Functional studies revealed that treating iNOS-negative/CXCL10-positive melanoma cell lines with a NO donor suppressed the expression of CXCL10. Furthermore, scavenging NO from iNOS-expressing cell lines significantly affected the chemokine expression profile. Culture supernatants from NO scavenger-treated melanoma cells promoted the migration of plasmacytoid dendritic cells, which was diminished when the cells were treated with a CXCL10-neutralizing antibody. CXCL10 has been reported to be an antitumorigenic chemokine. Our study suggests that the production of NO by iNOS inhibits the expression of CXCL10 in melanoma cells and leads to a protumorigenic tumor microenvironment. Inhibiting NO induces an antitumorigenic environment, and thus, iNOS should be considered to be an important therapeutic target in melanoma.
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