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CXCR4/CXCR7/CXCL12 axis promotes an invasive phenotype in medullary thyroid carcinoma.

CXCR4/CXCR7/CXCL12 axis promotes an invasive phenotype in medullary thyroid carcinoma.
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Werner TA, Forster CM, Dizdar L, Verde PE, Raba K, Schott M, Knoefel WT, Krieg A,


Werner TA, Forster CM, Dizdar L, Verde PE, Raba K, Schott M, Knoefel WT, Krieg A, (click to view)

Werner TA, Forster CM, Dizdar L, Verde PE, Raba K, Schott M, Knoefel WT, Krieg A,

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British journal of cancer 2017 11 07() doi 10.1038/bjc.2017.364

Abstract
BACKGROUND
Medullary thyroid carcinoma (MTC) is a rare and challenging endocrine malignancy. Once spread, the therapeutic options are limited and the outcome poor. For these patients, the identification of new druggable biological markers is of great importance. Here, we investigated the prognostic and biological role of the C-X-C chemokine receptors type 4 and 7 (CXCR4/7) in MTC.

METHODS
Eighty-six MTC and corresponding non-neoplastic thyroid specimens were immunohistochemically stained for CXCR4/7 using tissue microarray technology and expression levels correlated with clinicopathological variables. Medullary thyroid carcinoma cell line TT was treated with recombinant human SDF1α/CXCL12 (rh-SDF1α) and CXCR4 antagonists AMD3100 and WZ811. Changes in cell cycle activation, tumour cell invasiveness as well as changes in mRNA expression levels of genes associated with epithelial-mesenchymal transition (EMT) were investigated.

RESULTS
High CXCR4 expression was associated with large tumour size and metastatic disease. CXCR4 antagonists significantly reduced tumour cell invasiveness, while the treatment with rh-SDF1α stimulated invasive growth, caused cell cycle activation and induced EMT.

CONCLUSIONS
The CXCR4/CXCR7/CXCL12 axis plays an important role in MTC. We provide first evidence that the chemokine receptors might serve as potential therapeutic targets in patients with advanced MTC and offer new valuable insight into the underlying molecular machinery of metastatic MTC.British Journal of Cancer advance online publication, 7 November 2017; doi:10.1038/bjc.2017.364 www.bjcancer.com.

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