The CXCR4/CXCL12 axis in endometrial cancer
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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 (P = 0.035) whereas CXCL12 was overexpressed in normal mucosae (P = 0.002). CXCR4 expression (P = 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.
KeywordsChemokines Chemokine receptors CXCR4 CXCL12 CXCR7 Endometrial cancer
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.
- 2.Williams JW, Hirschowitz L (2006) Assessment of uterine wall thickness and position of the vascular plexus in the deep myometrium:implications for the measurement of depth of myometrial invasion of endometrial carcinomas. Int J Gynecol Pathol 25:59–64. doi: 10.1097/01.pgp.0000177123.78932.1d PubMedCrossRefGoogle Scholar
- 8.Broxmeyer HE, Cooper S, Kohli L et al (2003) Transgenic expression of stromal cell-derived factor-1/CXC chemokine ligand 12 enhances myeloid progenitor cell survival/antiapoptosis in vitro in response to growth factor withdrawal and enhances myelopoiesis in vivo. J Immunol (Baltimore, MD: 1950) 170:421–429Google Scholar
- 16.Koizumi K, Kozawa Y, Ohashi Y et al (2007) CCL21 promotes the migration and adhesion of highly lymph node metastatic human non-small cell lung cancer Lu-99 in vitro. Oncology Rep 17:1511–1516Google Scholar
- 33.Zeelemberg IS, Ruuls-Van Stalle S et al (2003) The chemokine receptor CXCR4 is required for outgrowth of colon carcinoma micrometastases. Cancer Res 63:3833–3839Google Scholar