Related Experiment Video
Updated: Feb 19, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
CXCR4/CXCR7/CXCL12 axis promotes an invasive phenotype in medullary thyroid carcinoma
Thomas A Werner1, Christina M Forster1, Levent Dizdar1
1Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, Duesseldorf 40225, Germany.
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.
Insights
The C-X-C chemokine receptor 4 (CXCR4) shows high expression in advanced medullary thyroid carcinoma (MTC), promoting metastasis. Targeting CXCR4 offers a promising therapeutic strategy for MTC patients.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Medullary thyroid carcinoma (MTC) is a rare endocrine malignancy with limited treatment options for advanced stages.
- Identifying new therapeutic targets is crucial for improving outcomes in metastatic MTC.
- The role of C-X-C chemokine receptors type 4 and 7 (CXCR4/7) in MTC progression was investigated.
Purpose of the Study:
- To investigate the prognostic and biological role of CXCR4 and CXCR7 in medullary thyroid carcinoma.
- To explore the potential of CXCR4/7 as therapeutic targets in advanced MTC.
Main Methods:
- Immunohistochemical staining of 86 MTC specimens for CXCR4/7.
- Correlation of expression levels with clinicopathological variables.
- In vitro studies using MTC cell lines treated with CXCL12 and CXCR4 antagonists to assess cell cycle, invasiveness, and epithelial-mesenchymal transition (EMT) gene expression.
Main Results:
- High CXCR4 expression correlated with larger tumour size and metastatic disease.
- CXCR4 antagonists reduced tumour cell invasiveness.
- CXCL12 stimulation promoted invasive growth, cell cycle activation, and induced EMT.
Conclusions:
- The CXCR4/CXCR7/CXCL12 axis is significantly involved in MTC.
- CXCR4/7 receptors represent potential therapeutic targets for advanced MTC.
- These findings provide new insights into the molecular mechanisms of metastatic MTC.
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