Medical Oncology

, Volume 29, Issue 3, pp 1468–1476

Impairment of breast cancer cell invasion by COX-2-specific inhibitor NS398: roles of CXCR4 and of uPA system

Authors

    • Department of Medical Genetics and CIMAGO, Faculty of MedicineUniversity of Coimbra
  • Vera Alves
    • Central Laboratory of Cytometry and CIMAGO, Faculty of MedicineUniversity of Coimbra
  • Luis Alcides Mesquita Nogueira
    • Department of Medical Genetics and CIMAGO, Faculty of MedicineUniversity of Coimbra
  • Manuel Santos Rosa
    • Central Laboratory of Cytometry and CIMAGO, Faculty of MedicineUniversity of Coimbra
  • Lina Carvalho
    • Department of Pathology and CIMAGO, Faculty of MedicineUniversity of Coimbra
  • Fernando Regateiro
    • Department of Medical Genetics and CIMAGO, Faculty of MedicineUniversity of Coimbra
Original Paper

DOI: 10.1007/s12032-011-9995-8

Cite this article as:
Silva, H.C., Alves, V., Nogueira, L.A.M. et al. Med Oncol (2012) 29: 1468. doi:10.1007/s12032-011-9995-8

Abstract

Inhibition of cyclooxygenase-2 (COX-2) is known to impair cancer cell metastatic behaviour, but the mechanisms involved largely remain elusive. We aimed to analyse whether the antimetastatic effect of COX-2 inhibition in breast cancer cells could be explained by variations in the expression levels of chemokine receptor CXCR4, vascular endothelium growth factor (VEGF) and UPA/UPAR components of the urokinase plasminogen activator system (uPAR). Breast cancer cell line MDA-MB-231 was exposed to COX-2-specific inhibitor NS398. Experimental data were assessed using Matrigel invasion tests, qRT-PCR, ELISA, flow cytometry and MTT test. Exposure to NS398 had no major effect on cell viability, apoptosis or VEGF production. Cell invasion was significantly decreased with reductions ranging from of 3.6% with 10 μM NS398 to 81.04% with 100 μM NS398. CXCR4 membrane expression was significantly reduced by 18% (P < 0.05) when cells were treated with 100 μM of NS398 for 72 h. UPA mRNA levels were significantly reduced to 78 and 63% after treatment with 10 μM NS398 for 48 and 72 h, respectively (P < 0.05). UPAR mRNA levels also decreased with mild NS398 concentrations, reaching the lowest level of 56% with 50 μM of NS398 for 48 h (P < 0.05). With NS398 higher concentrations, UPAR and UPA expression levels increased. According to our results, impairment of expression of CXCR4, UPA and UPAR differentially contribute to the antimetastatic effect of COX-2 inhibitors depending on drug concentration.

Keywords

COX-2Breast cancerMetastasisCXCR4UPAVEGF

Copyright information

© Springer Science+Business Media, LLC 2011