The high expression of inducible nitric oxide synthase (NOS2) by myeloid-derived suppressor cells (MDSCs) is a key mechanism of immune evasion in cancer.
Aberrant nitric oxide synthase 2 (NOS2) expression has been suggested as an interesting therapeutic target that is being implicated as a component of the molecular profile of several human malignant tumors, including glioblastoma, which is the most aggressive brain tumor with limited therapeutic options and poor prognosis.
Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is an obviously heterogeneous and highly invasive malignancy without definite phenotype.
Here, we investigated the NOS2 mRNA expression by reverse transcription-PCR in human glioma primary cultures at several grade of malignancy and glioma stem cell (GSC) derived neurospheres.
Given the evidence of a strong association between inflammation and pancreatic cancer and clinical evidence, which suggests an association between NOS2 and disease aggressiveness, it is critical to define the role of NO<sup>•</sup> signaling in this lethal malignancy.
The primary aim of this study is to characterize hepatocellular malignant neoplasm, NOS (HEMNOS), a new provisional entity describing a subset of paediatric hepatocellular tumours, which have histological features of neither typical hepatoblastoma (HB) nor hepatocellular carcinoma (HCC).
In many cases, elevated NOS2 has been shown to predict poor outcome in cancer such as ER- breast cancer, glioma, melanoma, cervical, liver, ovarian, and pancreatic.
Taken together, these findings showed that NOS2 is a predictor of prognosis in early stage, resected PDAC patients, and provide proof-of-principle that targeting NOS2 may have potential therapeutic value in this lethal malignancy.
It has also been suggested that high NO synthesis, secondary to inducible NO synthase (iNOS) expression, is a distinctive feature of cancer stem cells (CSCs), a small subset of tumour cells with self-renewal capacity.
Selective iNOS (1400 W) and pan-NOS (L-NMMA and L-NAME) inhibitors diminished cell proliferation, cancer stem cell self-renewal, and cell migration in vitro, together with inhibition of EMT transcription factors (Snail, Slug, Twist1, and Zeb1).
The results indicated that the polymorphisms in iNOS gene (C150T(Ser(608) Leu) polymorphism and polymorphic (CCTTT)n repeats) had no association with cancer risk for all genetic models.
The effect of NO in cancer depends on the activity and localization of NOS isoforms, concentration and duration of NO exposure, cellular sensitivity, and hypoxia/re-oxygenation process.
Furthermore, iNOS gene-mediated enhancement of cisplatin-mediated antitumor effects in lung cancer may be related to the attenuation of p-mTOR, MMP2 and the activation of p-p53.
A key component of inflammation promoting cancer is the transcription factor NF-κB, which is known to play a critical role in the regulation of the inducible nitric oxide synthase (iNOS) gene. iNOS is an enzyme dominantly expressed during inflammatory reactions.
Many studies have demonstrated the function of nitric oxide (NO) or nitric oxide synthase-2 (NOS-2) in cancer as pro-neoplastic or anti-neoplastic effectors, but the role of NO and NOS-2 in hepatocellular carcinoma (HCC) remains unclear.
The aim of this study was to evaluate the association of NOS2 polymorphisms rs2297518" genes_norm="4843">Ser608Leu (rs2297518) in exon 16, -954G/C and -1173C/T, both in the promoter region, with gastric cancer and chronic gastritis and the association of cancer with risk factors such as smoking, alcohol intake and H. pylori infection.
Tumors formed in the tongues of SCID mice xenografted with OSC-4, NOS-2, and OSC-7 immunohistochemically revealed strong, moderate, and weak expression of laminin-5 gamma2 chains, respectively, and laminin-5 gamma2 chains were secreted in the conditioned medium of the cancer cells in parallel with the in vivo results.
The ATB(0,+) mRNA increased 22.9+/-3.0-fold in colorectal cancer compared to normal tissue and the increase was evident in each of the 10 cases examined. iNOS mRNA increased 5.2+/-1.1-fold in cancer specimens.
Our findings help clarify the role of steroid hormones in NOSII expression as well as the effect on cell viability and may suggest novel approaches towards hormonotherapy and the treatment of cancer.