In vitro characterization and inhibition of the CXCR4/CXCL12 chemokine axis in human uveal melanoma cell lines

In vitro characterization and inhibition of the CXCR4/CXCL12 chemokine axis in human uveal melanoma cell lines

Author Di Cesare, Sebastian Google Scholar
Marshall, Jean-Claude Google Scholar
Fernandes, Bruno F. Google Scholar
Logan, Patrick Google Scholar
Antecka, Emilia Google Scholar
Bravo Filho, Vasco Google Scholar
Burnier Júnior, Miguel Noel Nascente Autor UNIFESP Google Scholar
Institution McGill Univ
Universidade Federal de São Paulo (UNIFESP)
Abstract Purpose: the CXCR4/CXCL12 chemokine axis may play a critical role in guiding CXCR4+ circulating malignant cells to organ specific locations that actively secrete its ligand CXCL12 (SDF-1) such as bone, brain, liver, and lungs. We sought to characterize the presence of the CXCR4/CXCL12 axis in five uveal melanoma (UM) cell lines in vitro. the ability of TN14003, a synthetic peptide inhibitor that targets the CXCR4 receptor complex, to inhibit this axis was also assessed.Methods: Immunocytochemistry was performed against CXCR4 to confirm expression of this chemokine receptor in all five UM cell lines. Flow cytometry was preformed to evaluate CXCR4 cell surface expression on all five UM cell lines. A proliferation assay was also used to test effects TN14003 would have on cellular proliferation. Inhibition of cellular migration by specifically inhibiting the CXCR4/CXCL12 axis with TN14003 was also investigated. the binding efficacy of TN14003 to the CXCR4 receptor was assessed through flow cytometric methods.Results: the CXCR4 receptor was present on all five UM cell lines. All five cell lines expressed different relative levels of surface CXCR4. TN14003 did not affect the proliferation of the five cell lines (p > 0.05). All cell lines migrated towards the chemokine CXCL12 at a level greater than the negative control (p < 0.05). All 5 cell lines pre-incubated with TN14003 prevented cellular migration towards chemokine CXCL12 (p < 0.01). TN14003 preferentially binds CXCR4 to native ligand CXCL12.Conclusion: Interfering with the CXCR4/CXCL12 axis, using TN14003 was shown to effectively down regulate UM cell migration in vitro. Knowing that UM expresses the CXCR4 receptor, these CXCR4+ cells may be less likely to colonize distant organs that secrete the CXCL12 ligand, if treated with an inhibitor that binds CXCR4. Further studies should be pursued in order to test TN14003 efficacy in vivo.
Language English
Sponsor Cedar's Cancer Institute
Date 2007-01-01
Published in Cancer Cell International. London: Biomed Central Ltd, v. 7, 7 p., 2007.
ISSN 1475-2867 (Sherpa/Romeo, impact factor)
Publisher Biomed Central Ltd
Extent 7
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000208405100017

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