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The CXCR4/CXCL12 axis in endometrial cancer

  • Stefania Gelmini
  • Monica Mangoni
  • Francesca Castiglione
  • Cristina Beltrami
  • Annalisa Pieralli
  • Karin Louise Andersson
  • Massimiliano Fambrini
  • Gian Luigi Taddei
  • Mario Serio
  • Claudio OrlandoEmail author
Research Paper

Abstract

Chemokines and their receptors seem to act as important regulators of the metastatic cascade. CXCL12 and its receptor CXCR4 were shown to be involved in human cancer progression. There is increasing evidences suggesting that the expression of CXCR4 in human cancers is correlated with poor patient prognosis and that CXCR4 neutralization can prevent metastases in vivo. Here we tested the role of the CXCR4/CXCL12 axis in a neoplasia with a reduced risk of metastatic progression, such as human endometrial cancer. CXCR4 and CXCL12 mRNA expression was measured in 41 endometrial cancers and in corresponding not affected tissues. The expression of CXCR4 was predominant in endometrial cancer (= 0.035) whereas CXCL12 was overexpressed in normal mucosae (= 0.002). CXCR4 expression (= 0.035), but not CXCL12, was significantly related to cancer differentiation. Endometrial cancer cells (HEC1A) were able to generate diffuse metastases in peritoneum, lung and liver of CD-1 nude mice, but the simultaneous treatment with a neutralizing anti-CXCR4 monoclonal antibody dramatically reduced the number and the size of metastases in the animals. In conclusion, our data seem to indicate that the CXCR4-CXCL12 axis can play a role in the progression of endometrial carcinoma and that specific therapies with antagonists of chemokines receptors could be of help in the treatment of metastatic patients.

Keywords

Chemokines Chemokine receptors CXCR4 CXCL12 CXCR7 Endometrial cancer 

Notes

Acknowledgments

This study was partially supported by a grant from the Italian Ministry of Scientific Research (MIUR). The authors wish to thank Dr. Adriana Lombardi for the accurate revision of manuscript content and language.

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Stefania Gelmini
    • 1
  • Monica Mangoni
    • 2
  • Francesca Castiglione
    • 3
  • Cristina Beltrami
    • 1
  • Annalisa Pieralli
    • 4
  • Karin Louise Andersson
    • 4
  • Massimiliano Fambrini
    • 4
  • Gian Luigi Taddei
    • 3
  • Mario Serio
    • 1
  • Claudio Orlando
    • 1
    Email author
  1. 1.Department of Clinical Pathophysiology, Clinical Biochemistry UnitUniversity of FlorenceFlorenceItaly
  2. 2.Department of Clinical Pathophysiology, Radiotherapy UnitUniversity of FlorenceFlorenceItaly
  3. 3.Department of Human Pathology and OncologyUniversity of FlorenceFlorenceItaly
  4. 4.Department of Gynecology, Perinatology and Human ReproductionUniversity of FlorenceFlorenceItaly

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