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Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells
Published on: March 16, 2017
Sarcomas often express constitutive nitric oxide synthases (NOS) but infrequently inducible NOS
Isabela W Cunha1, Ademar Lopes, Roberto Falzoni
1Department of Anatomic Pathology, Medical and Research Centre, Hospital do Cancer A. C. Camargo, São Paulo, Brazil. iwcancer@hcancer.org.br
Abstract:
Nitric oxide (NO) has a dual action in tumors, with both pro-tumor and anti-tumor activities. NO is produced by nitric oxide synthases (NOS). There are three enzyme isoforms: two of them are constitutively produced (neuronal or brain NOS and endothelial NOS), and one is an inducible form (iNOS). NOS expression has been shown in several epithelial tumors, but there is no report addressing NOS expression in sarcomas. The authors evaluated the expression of NOS in 97 cases of various sarcomas spotted in duplicate in a tissue array paraffin block. Eighty-four of the 97 tumor specimens (86.6%) expressed nNOS, and most of them showed a strong expression of the isoenzyme. Only chondrosarcomas and liposarcomas had significant numbers of negative cases, and all pleomorphic sarcomas, alveolar soft part sarcomas, angiosarcomas, gastrointestinal stromal tumors, and synovial sarcomas showed some degree of positivity. Forty-three cases (44.4%) showed eNOS immunostaining, but only 15.5% showed a strong signal, with emphasis on angiosarcomas, chondrosarcomas, alveolar soft part sarcomas, and synovial sarcoma. Strong expression of iNOS was observed in only 9 cases (9.3%), with weak expression in another 26 cases (26.8%). Strong expression of iNOS was found in malignant peripheral nerve sheet tumors, liposarcomas, pleomorphic sarcomas, fibrosarcomas, chondrosarcomas, and synovial sarcomas. Apparently alveolar soft part sarcomas are unusual in their capacity of expression of NOS isoforms, and in a very peculiar pattern. In conclusion, sarcomas in general commonly express constitutive NOS, and only a few types of sarcomas can express iNOS, the isoenzymes capable of releasing large amounts of NO. More comprehensive studies should be performed to better understand the clinical importance of NOS expression and NO production in sarcomas.
Insights
Nitric oxide synthases (NOS) are commonly expressed in sarcomas, particularly constitutive isoforms like nNOS. Inducible NOS (iNOS) expression is less common but found in specific sarcoma types, warranting further clinical investigation.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Nitric oxide (NO) exhibits dual roles in tumor progression, acting as both a pro-tumor and anti-tumor agent.
- Nitric oxide is synthesized by three main isoforms of nitric oxide synthases (NOS): neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS).
- While NOS expression is documented in epithelial tumors, its presence in sarcomas remains largely uninvestigated.
Purpose of the Study:
- To investigate the expression patterns of nNOS, eNOS, and iNOS in a diverse cohort of human sarcoma specimens.
- To identify specific sarcoma subtypes that exhibit significant expression of different NOS isoforms.
- To lay the groundwork for understanding the potential clinical relevance of NOS and NO in sarcoma biology.
Main Methods:
- Utilized tissue array technology to analyze NOS expression in 97 diverse sarcoma cases.
- Performed immunohistochemical staining to detect the presence and intensity of nNOS, eNOS, and iNOS.
- Quantified and categorized NOS expression levels across different sarcoma subtypes.
Main Results:
- A high prevalence of nNOS expression (86.6%) was observed across most sarcomas, with notable exceptions in chondrosarcomas and liposarcomas.
- eNOS immunostaining was detected in 44.4% of cases, with strong signals predominantly in angiosarcomas, chondrosarcomas, alveolar soft part sarcomas, and synovial sarcomas.
- iNOS expression was less frequent, with strong signals in 9.3% and weak signals in 26.8% of cases, particularly noted in malignant peripheral nerve sheath tumors, liposarcomas, and synovial sarcomas.
Conclusions:
- Sarcomas generally exhibit common expression of constitutive NOS isoforms, primarily nNOS.
- Inducible NOS (iNOS) expression is restricted to a subset of sarcoma types, suggesting a potential role in specific tumor microenvironments.
- Further research is essential to elucidate the clinical significance of NOS expression and NO production in sarcomas.
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