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Interrelated overexpression of endothelial and inducible nitric oxide synthases, endothelin‐1 and angiogenic factors in human papillary thyroid carcinoma
Author(s) -
Donckier Julian E.,
Michel Luc,
Delos Monique,
Havaux Xavier,
Van Beneden Ronald
Publication year - 2006
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2006.02535.x
Subject(s) - endocrinology , medicine , thyroid carcinoma , carcinogenesis , receptor , endothelin 1 , thyroid cancer , vascular endothelial growth factor , thyroiditis , thyroid , immunohistochemistry , angiogenesis , angiopoietin receptor , endothelin receptor , chemistry , biology , cancer , vegf receptors
Summary Objective Nitric oxide (NO) and endothelin‐1 (ET‐1) are involved in carcinogenesis. Overexpression of the ET‐1 axis has been demonstrated in papillary thyroid carcinoma (PTC). This study investigated the expression of NO synthases (NOS) and their relationship with expression of ET‐1 and angiogenic markers in PTC. Design and Patients Expression of NOS, angiogenic markers [vascular endothelial growth factor (VEGF), angiopoietin‐1 and angiopoietin‐2] and their receptors was studied in surgical thyroid samples obtained from 22 patients aged 15–68 years. Three groups were constituted: normal thyroid ( n = 5), Hashimoto's thyroiditis ( n = 9) and PTC ( n = 8). Results Immunohistochemistry disclosed NOS2 and NOS3 immunoreactivity in PTC cells, the percentage of positive cells being greater than normal ( P < 0·02). Real‐time quantitative polymerase chain reaction (RTQ‐PCR) showed that NOS2 and NOS3 mRNA levels were, respectively, increased ( P < 0·02) by 2·6 ± 0·6 and 4·2 ± 1·1 times in PTC. RTQ‐PCR demonstrated that VEGF, its receptors VEGFR‐1 and VEGFR‐2, and angiopoietin‐2 and its receptor (Tie2) were also overexpressed ( P < 0·05) in PTC. Correlations were found between ET‐1 expression and that of NOS2, angiopoietin‐1 and ‐2 ( P < 0·05). NOS2 mRNA levels also correlated with those of NOS3 and angiopoietin‐2 ( P < 0·05). In thyroiditis, NOS2 immunoreactivity was observed in inflammatory cells whereas NOS2 mRNA levels were 12·1 ± 1·6 times higher than normal ( P < 0·005). Conclusions This study revealed an activation of the NO pathway in thyroid carcinoma, which is interrelated to the ET‐1 axis, both systems being overexpressed in concert with angiogenic factors. This global system might play a role in carcinogenesis and constitutes a potential target for anticancer therapy.