title: The CXCR4/CXCL12 axis in endometrial cancer.
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 (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.
authors.affiliation: Department of Clinical Pathophysiology, Clinical Biochemistry Unit, University of Florence, Viale Pieraccini 6, Florence, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gelmini
authors.forename: Monica
authors.initials: M
authors.lastname: Mangoni
authors.forename: Francesca
authors.initials: F
authors.lastname: Castiglione
authors.forename: Cristina
authors.initials: C
authors.lastname: Beltrami
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pieralli
authors.forename: Karin Louise
authors.initials: KL
authors.lastname: Andersson
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Fambrini
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Taddei
authors.forename: Mario
authors.initials: M
authors.lastname: Serio
authors.forename: Claudio
authors.initials: C
authors.lastname: Orlando
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000556:secondary; D054387:Receptors, CXCR / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: C501896:ACKR3 protein, human; D000911:Antibodies, Monoclonal; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D019718:Receptors, CXCR4