Inducible nitric oxide synthase: correlation with extracapsular spread and enhancement of tumor cell invasion in head and neck squamous cell carcinoma

Head Neck. 2008 Feb;30(2):208-14. doi: 10.1002/hed.20675.


Background: Extracapsular nodal spread is a major prognostic indicator in head and neck cancer. Nitric oxide (NO), primarily produced by the enzyme inducible NO synthase (iNOS), has a large number of actions in cancer biology, but no studies have investigated its possible role in extracapsular spread or tumor invasion.

Methods: Immunochemistry was used to study iNOS expression in 48 patients with either extracapsular or encapsulated metastasis. In vitro invasion assays were performed using H357 (an oral squamous cell carcinoma cell line) using the iNOS inhibitor drug, 1400 W.

Results: iNOS expression was significantly associated with extracapsular spread, with 22/27 cases showing positive iNOS expression compared with 8/21 cases in the encapsulated group (p = .01). Invasion of H357 cells was inhibited by 1400 W at concentrations of 100 microM and 1 mM (p = .002, p = .003).

Conclusion: iNOS protein seems to be associated with extracapsular spread and invasion in head and neck cancer. Further studies are required to understand this role more fully.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology*
  • Female
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Nitric Oxide Synthase Type II / metabolism*
  • Tumor Cells, Cultured


  • Nitric Oxide Synthase Type II