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The CXCR4/CXCL12 axis in endometrial cancer
Stefania Gelmini1, Monica Mangoni, Francesca Castiglione
1Department of Clinical Pathophysiology, Clinical Biochemistry Unit, University of Florence, Viale Pieraccini 6, Florence, Italy.
Clinical & Experimental Metastasis
|February 10, 2009
Summary
The CXCR4-CXCL12 axis plays a role in endometrial cancer progression. Neutralizing CXCR4 (C-X-C motif chemokine receptor 4) significantly reduced metastases in preclinical models, suggesting targeted therapies for metastatic patients.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Chemokines and their receptors regulate cancer metastasis.
- The CXCL12/CXCR4 axis is implicated in various human cancers, with CXCR4 expression linked to poor prognosis.
- CXCR4 neutralization has shown potential in preventing metastasis in vivo.
Purpose of the Study:
- To investigate the role of the CXCL12/CXCR4 axis in human endometrial cancer, a cancer type with lower metastatic risk.
- To determine the expression levels of CXCR4 and CXCL12 in endometrial tumors and normal tissues.
- To evaluate the therapeutic potential of targeting CXCR4 in preclinical models of endometrial cancer metastasis.
Main Methods:
- Quantitative analysis of CXCR4 and CXCL12 mRNA expression in 41 endometrial cancers and adjacent normal tissues.
- Correlation analysis between CXCR4/CXCL12 expression and clinicopathological features, including cancer differentiation.
- In vivo metastasis model using human endometrial cancer cells (HEC1A) in CD-1 nude mice, treated with anti-CXCR4 monoclonal antibody.
Main Results:
- CXCR4 mRNA expression was significantly higher in endometrial cancer tissues compared to normal tissues (P = 0.035).
- CXCL12 was overexpressed in normal mucosae (P = 0.002), while CXCR4 expression correlated with poorer cancer differentiation (P = 0.035).
- Treatment with an anti-CXCR4 antibody markedly reduced the number and size of peritoneal, lung, and liver metastases in mice.
Conclusions:
- The CXCR4-CXCL12 axis is implicated in the progression of endometrial carcinoma.
- CXCR4 expression is a potential biomarker for poor prognosis and differentiation in endometrial cancer.
- Targeting the CXCR4-CXCL12 axis with receptor antagonists may offer a therapeutic strategy for metastatic endometrial cancer.
