© 1998 by Oxford University Press
Journal Of The National Cancer Institute, Vol 90, 587-596, Copyright © 1998 by Oxford University Press
O Gallo, E Masini, L Morbidelli, A Franchi, I Fini-Storchi, WA Vergari and M Ziche
BACKGROUND: Angiogenesis (formation of new blood vessels) is associated
with tumor growth and metastasis in patients with solid tumors, including
those of the head and neck. Nitric oxide (NO) production may contribute to
these processes. We assessed the role of the NO pathway in angiogenesis and
tumor progression in patients with head and neck cancer. METHODS:
Biochemical assays were used to measure NO synthase (NOS) activity and
cyclic guanosine monophosphate (cGMP) levels in specimens of tumor and
normal mucosa obtained from 27 patients. Microvessels in tumor specimens
were identified by CD-31-specific immunohistochemical staining.
Associations between microvessel densities, levels of NOS, and cGMP were
examined by use of two-sided statistical tests. Tumor specimens and human
squamous carcinoma A-431 cells were grown as explants on the corneas of
rabbits, and the effect of the NOS inhibitor
N(omega)-nitro-L-arginine-methyl ester (L-NAME) was tested. RESULTS: Levels
of total NOS, inducible NOS, and cGMP were higher in tumor specimens than
in specimens of normal mucosa (all P<.0001). Tumor specimens from
patients with lymph node metastases presented a higher total NOS activity
(P = .005) and were markedly more vascularized than tumor specimens from
patients with no lymph node involvement (P = .0002). Microvessel density at
the tumor edge was an independent predictor of metastasis for this series
of patients (odds ratio = 1.19; 95% confidence interval = 1.07-2.89; P =
.04). A-431 cells and tumor specimens exhibiting high levels of NOS
activity induced angiogenesis in the rabbit cornea assay; when NO
production was blocked, tumor angiogenesis and growth were repressed.
CONCLUSIONS: The NO pathway appears to play a key role in tumor
angiogenesis and spread in patients with head and neck cancer.
ARTICLES
Role of nitric oxide in angiogenesis and tumor progression in head and neck cancer
Institute of Otolaryngology Head and Neck Surgery, University of Florence, Italy.
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