Type II nitric oxide synthase (NOS2) expression correlates with lymph node status in oral squamous cell carcinoma

Abstract

In tumour biology, nitric oxide (NO) has a complex array of concentration-dependent actions, including both inhibitory and promoting effects. It is thought that the levels of NO found in many human cancers lead to enhanced angiogenesis and tumour dissemination. In the current study, we assessed the immunohistochemical expression of the enzyme type II nitric oxide synthase (NOS2) in 41 cases of oral squamous cell carcinoma and correlated the findings with lymph node status. A significant relationship was found between NOS2 expression and lymph node metastasis (P<0.0002). Furthermore, lymph node metastasis correlated with the degree and intensity of staining seen (P<0.001). No correlation was found between the size of the primary tumour, degree of tumour differentiation or smoking status and NOS2 staining. Western blotting confirmed NOS2 protein expression in select cases. As with many other human tumours, NOS2 is not a ubiquitous finding in oral cancer. Its expression may be of value in assessing lymph node status prior to surgery, and it represents a target for possible therapeutic manipulation.

In vitro effects of nitric oxide synthase inhibitor L-NAME on oral squamous cell carcinoma: a preliminary study

“…Although it is now becoming increasingly evident that NO itself probably promotes growth of human tumours by facilitating both angiogenesis and dissemination 8,11 , little is known about the effect of NOS-released NO on tumour cells themselves. In the present study, it was found for the first time that L-NAME, an active NOS inhibitor, could partly inhibit TSCCa cells both concentration and…”

Nitric Oxide Is a Factor in the Stabilization of Hypoxia-Inducible Factor-1α in Cancer: Role of Free Radical Formation

“…Immunohistochemistry for inducible NOS (iNOS), endothelial NOS (eNOS), and HIF-1a proteins was carried out on 29 formalin-fixed specimens of human oral squamous cell carcinoma and 10 samples of normal oral mucosa. Monoclonal antibodies to iNOS, eNOS (BD Biosciences, Oxford, United Kingdom), and HIF-1a (Novus Biologicals, Littleton, CO) were used as previously described (16,17), and samples were developed using an avidin biotin horseradish peroxidase system (DAKO, Glostrup, Denmark). Positive controls were normal kidney for HIF-1a and an oral squamous cell carcinoma known to have high eNOS expression and activity.…”

“…In those experiments, however, NO was either added exogenously or generated in an overexpressed cell system. In view of this, we decided to investigate whether endogenous NO is involved in the presence of HIF-1a in human oral squamous cell carcinoma, a malignancy in which both HIF-1a and NO are known to occur (10,16). To do this, we studied the distribution of NO synthase (NOS) and of HIF-1a in samples of human oral carcinoma tissue and in cell lines obtained from human oral squamous cell carcinoma, where we also investigated the effect of free radical production on HIF-1a expression.…”

Part II. Initial molecular and cellular characterization of high nitric oxide-adapted human tongue squamous cell carcinoma cell lines

“…Correlation between NOS expression and tumor progression, including lymph node metastases, has been reported in human oral squamous cell carcinoma [9,35], gastric carcinoma [36], and breast cancer [37]. Breast cancer patients testing positive for iNOS were found to have significantly lower 5-year survival rate than patients who tested negative for iNOS [37].…”