CXCR4 expression in papillary thyroid carcinoma: induction by nitric oxide and correlation with lymph node metastasisReportar como inadecuado

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BMC Cancer

, 8:274

First Online: 30 September 2008Received: 27 June 2008Accepted: 30 September 2008DOI: 10.1186-1471-2407-8-274

Cite this article as: Yasuoka, H., Kodama, R., Hirokawa, M. et al. BMC Cancer 2008 8: 274. doi:10.1186-1471-2407-8-274


BackgroundMetastasis to regional lymph nodes is a common step in the progression of cancer. Recent evidence suggests that tumor production of CXCR4 promotes lymph node metastasis. Nitric oxide NO may also increase metastatic ability in human cancers.

MethodsNitrite-nitrate levels and functional CXCR4 expression were assessed in K1 and B-CPAP papillary thyroid carcinoma PTC cells after induction and-or inhibition of NO synthesis. CXCR4 expression was also analyzed in primary human PTC. The relationship between nitrotyrosine levels, which are a biomarker for peroxynitrate formation from NO in vivo, CXCR4 expression, and lymph node status was also analyzed.

ResultsProduction of nitrite-nitrate and functional CXCR4 expression in both cell lines was increased by treatment with the NO donor DETA NONOate. The NOS inhibitor L-NAME eliminated this increase. Positive CXCR4 immunostaining was observed in 60.7% 34-56 of PTCs. CXCR4 expression was significantly correlated with nitrotyrosine levels and lymph node metastasis in human PTC.

ConclusionOur data indicate that NO stimulates CXCR4 expression in vitro. Formation of the NO biomarker nitrotyrosine was also correlated with CXCR4 expression and lymph node metastasis in human PTC. NO may induce lymph node metastasis via CXCR4 induction in papillary thyroid carcinoma.

AbbreviationsCXCRCXC chemokine receptor

PTCPapillary Thyroid Carcinoma

VEGFVascular Endothelial Growth Factor

NONitric Oxide

DMEMDulbecco-s Modified Eagle Medium

FCSFetal Calf Serum

L-NAMEN-nitro-L-arginine methyl ester

DETA NONOateZ-1-2-2-Aminoethyl-N-2-ammonioethylaminodiazen-1-ium-1,2-diolate

NOSNO synthases

PBSphosphate-buffered saline


PCRpolymerase chain reaction

GAPDHglyceraldehyde-3-phosphate dehydrogenase

rhCXCL12recombinant human CXCL12.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-8-274 contains supplementary material, which is available to authorized users.

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Autor: Hironao Yasuoka - Rieko Kodama - Mitsuyoshi Hirokawa - Yuuki Takamura - Akira Miyauchi - Tokio Sanke - Yasushi Nakamura


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