Table 1.
Nitrotyrosine presence in human cancers.
| Type of cancer | Nitrotyrosine staining pattern | Clinical and/or experimental correlation | NOS/ARG isoforms | Reference |
|---|---|---|---|---|
| Pancreatic adenocarcinoma | Increased staining for iNOS and nitrotyrosine in the ductal epithelium of pancreatic tumor tissue | Enhanced expression of FGF-1/2 and FGF receptors associated with an environment of oxidative stress. Tyrosine-nitrated c-Src found only in patient tissues | iNOS | (152) |
| Prostate cancer | Increased staining for nitrotyrosine in the epithelial cancer cells, some hot spots in the TILs | Dysfunctional in situ TIL responses | iNOS/ARG2 | (124) |
| Glioblastoma | Increased staining for nitrotyrosine in glioma cells and possibly in passenger leukocytes | Inhibition of wild-type p53 function in malignant glioma cells | NOS1/iNOS | (143, 153, 154) |
| Lung squamous cell carcinoma and well differentiated adenocarcinoma | Increased staining for nitrotyrosine in tumor cells but not in adjacent normal areas | Nitration of metabolic enzymes, structural proteins, and proteins involved in prevention of oxidative damage | NOS3/iNOS | (155) |
| Head and neck squamous cell carcinoma | Increased staining for nitrotyrosine in tumor cells | Increased nitrotyrosine staining in the progression of oral mucosa from normal to dysplastic and neoplastic changes | NOS3 and iNOS | (47, 156) |
| Mesothelioma | Diffuse and variable cytoplasmic nitrotyrosine staining for both cancer and stromal cells | More intense nitrotyrosine staining in mesotheliomas with higher mitochondrial manganese superoxide dismutase (MnSOD) expression | ND | (150) |
| Colon cancer | Cytoplasmic and nuclear nitrotyrosine staining in cancer and stromal cells | Reduction of PHA-dependent proliferation of human T lymphocytes in the presence of supernatant from a culture of cytokine-induced, NO-producing colon carcinoma cells | iNOS | (147, 157) |
| Breast cancer | Diffuse cytoplasmic and focal nuclear nitrotyrosine staining for cancer cells, stromal macrophages and neutrophils | Correlation between high nitrotyrosine staining and VEGF-C immunoreactivity and lymph node metastasis; nitrotyrosine staining proposed as an independent prognostic value for overall survival | ND | (149) |
| Melanoma | Weak to strong diffuse and paranuclear staining of melanoma cells | Strong correlation between poor survival with iNOS and nitrotyrosine expression by melanoma cells in patients with stage III disease | iNOS | (138) |
| Papillary thyroid carcinoma (PTC) | Weak to high-grade staining in the cytoplasm and focally in the nucleus in PTC cells | High-grade nitrotyrosine staining was correlated with VEGF-D immunoreactivity and lymph node metastasis | iNOS | (151, 158) |
| Bladder carcinoma | Nitrotyrosine staining mainly in endothelial cells and certain stromal cells of malignant bladder tumors; weak staining in tumor cells | ND | iNOS/NOS3 | (159) |
| Gastric adenocarcinoma | Cytoplasmic and nuclear nitrotyrosine staining in tumor and adjacent stromal cells | Expression of iNOS and nitrotyrosine with a high AI is associated with a poor survival; correlation of both iNOS and nitrotyrosine with cancer subtype (prevalence in tubular carcinoma) but no significance correlation with clinical parameters | iNOS | (148, 160) |
| Renal cancer | Nitrotyrosine staining mainly in tumor cells, but occasionally also in stroma and in the tubular cells of non-neoplastic renal tissue | Nitrotyrosine associated with high-grade tumors | ND | (161) |
| Gynecological cancer | Moderate nitrotyrosine cytoplasmic staining in most of invasive ovarian carcinomas | In invasive ovarian carcinomas there is no association with any clinico-pathological parameters, whereas it was observed a strong correlation with expression of the antioxidant enzymes peroxiredoxin IV and thioredoxin | iNOS | (162, 163) |
ND, not determined; 8-OHdG, 8-hydroxydeoxyguanosine; VEGF, vascular endothelial growth factor; MnSOD, mitochondrial manganese superoxide dismutase; TILs, tumor-infiltrating lymphocytes; AI, apoptotic index.