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PMID: 11326316 Published · ppublish English Journal Article

Cyclooxygenase-2 pathway correlates with VEGF expression in head and neck cancer. Implications for tumor angiogenesis and metastasis.

Neoplasia (New York, N.Y.) ·Vol. 3 ·No. 1 ·2001-00-00 ·Pages 53-61

Gallo O, Franchi A, Magnelli L, Sardi I, Vannacci A, Boddi V, Chiarugi V, Masini E

Abstract

We evaluated the role of COX-2 pathway in 35 head and neck cancers (HNCs) by analyzing COX-2 expression and prostaglandin E2 (PGE2) production in relation to tumor angiogenesis and lymph node metastasis. COX-2 activity was also correlated to vascular endothelial growth factor (VEGF) mRNA and protein expression. COX-2 mRNA and protein expression was higher in tumor samples than in normal mucosa. PGE2 levels were higher in the tumor front zone in comparison with tumor core and normal mucosa (P<.0001). Specimens from patients with lymph node metastasis exhibited higher COX-2 protein expression (P=.0074), PGE2 levels (P=.0011) and microvessel density (P<.0001) than specimens from patients without metastasis. A significant correlation between COX-2 and tumor vascularization (r(s)=0.450, P=.007) as well as between COX-2 and microvessel density with VEGF expression in tumor tissues was found (r(s)=0.450, P=.007; r(s)=0.620, P=.0001, respectively). The induction of COX-2 mRNA and PGE2 synthesis by EGF and Escherichia coli lipopolysaccharide (LPS) in A-431 and SCC-9 cell lines, resulted in an increase in VEGF mRNA and protein production. Indomethacin and celecoxib reversed the EGF- and LPS-dependent COX-2, VEGF, and PGE2 increases. This study suggests a central role of COX-2 pathway in HNC angiogenesis by modulating VEGF production and indicates that COX-2 inhibitors may be useful in HNC treatment.

MeSH Terms
Aged Blotting, Northern Blotting, Western Carcinoma, Squamous Cell/blood supply,enzymology,pathology Celecoxib Cyclooxygenase 2 Dinoprostone/metabolism Endothelial Growth Factors/genetics,metabolism Epidermal Growth Factor/pharmacology Escherichia coli Female Gene Expression Head and Neck Neoplasms/blood supply,enzymology,pathology Humans Immunoenzyme Techniques Indomethacin/pharmacology Isoenzymes/genetics,metabolism Lipopolysaccharides/pharmacology Lymph Nodes/enzymology Lymphatic Metastasis Lymphokines/genetics,metabolism Male Membrane Proteins Middle Aged Neovascularization, Pathologic/enzymology,pathology Prostaglandin-Endoperoxide Synthases/genetics,metabolism Pyrazoles RNA, Messenger/metabolism Signal Transduction Sulfonamides/pharmacology Tumor Cells, Cultured/drug effects,metabolism Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors
Chemicals
Endothelial Growth Factors Isoenzymes Lipopolysaccharides Lymphokines Membrane Proteins Pyrazoles RNA, Messenger Sulfonamides Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Epidermal Growth Factor Cyclooxygenase 2 PTGS2 protein, human Prostaglandin-Endoperoxide Synthases Celecoxib Dinoprostone Indomethacin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Gallo O
Department of Oto-Neuro-Ophthalmologic Surgery, University of Florence, 50139 Florence, Italy. o.gallo@dfc.unifi.it
Franchi A
Magnelli L
Sardi I
Vannacci A
Boddi V
Chiarugi V
Masini E
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Article Info
Journal
Neoplasia (New York, N.Y.)
Abbr.
Neoplasia
ISSN
1522-8002
DOI
10.1038/sj.neo.7900127
Email
o.gallo@dfc.unifi.it
Published
2001-00-00
Pages
53-61
Language
English
Region
United States
NLM ID
100886622
PMCID
PMC1505025
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.neo.7900127 PMC Full Text
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