The role of ecto-5′-nucleotidase/CD73 in glioma cell line proliferation
- 18 July 2008
- journal article
- Published by Springer Science and Business Media LLC in Molecular and Cellular Biochemistry
- Vol. 319 (1-2), 61-68
- https://doi.org/10.1007/s11010-008-9877-3
Abstract
Malignant gliomas are the most common and devastating primary tumors in the brain and, despite treatment, patients with these tumors have a poor prognosis. The participation of ecto-5′-NT/CD73 per se as a proliferative factor, being involved in the control of cell growth, differentiation, invasion, migration and metastasis processes has been previously proposed. In the present study, we evaluated the activity and functions of ecto-5′-NT/CD73 during the proliferation process of rat C6 and human U138MG glioma cell lines. Increasing confluences and culture times led to an increase in ecto-5′-NT/CD73 activity in both C6 and U138MG glioma cells. RT-PCR analysis and flow cytometry analysis showed a significant increase in ecto-5′-NT/CD73 mRNA and protein levels, respectively, comparing confluent with sub-confluent cultures in human U138MG glioma cells. Ecto-5′-nucleotidase/CD73 may regulate the extracellular adenosine 5′-monophosphate (AMP) and adenosine levels. Treatment with 1 μM APCP, a competitive ecto-5′-NT/CD73 inhibitor, caused a significant reduction of 30% in glioma cell proliferation. In addition, 100 μM adenosine increases cell proliferation by 36%, and the treatment with adenosine plus NBTI and dipyridamole, produced an additional and significant increase of on cell proliferation. The inhibitory effect on cell proliferation caused by APCP was reverted by co-treatment with NBTI and dipyridamole. AMP (1 mM and 3 mM) decreased U138MG glioma cell proliferation by 29% and 42%, respectively. Taken together, these results suggest the participation of ecto-5′-NT/CD73 in cell proliferation and that this process is dependent upon the enzyme’s production of adenosine, a proliferative factor, and removal of AMP, a toxic molecule for gliomas.Keywords
This publication has 41 references indexed in Scilit:
- RNA interference of ecto-5′-nucleotidase (CD73) inhibits human breast cancer cell growth and invasionClinical & Experimental Metastasis, 2007
- Molecularly targeted therapy for malignant gliomaCancer, 2007
- Epidemiology and molecular pathology of gliomaNature Clinical Practice Neurology, 2006
- Brain cancer stem-like cellsEuropean Journal of Cancer, 2006
- Glioma modelsBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2001
- The p21-Ras signal transduction pathway and growth regulation in human high-grade gliomasBrain Research Reviews, 1999
- T Cell Signalling Through CD73Cellular Signalling, 1997
- In vitro effect of extracellular AMP on MCF-7 breast cancer cells: Inhibition of glycolysis and cell proliferationJournal of Cellular Physiology, 1992
- A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye BindingAnalytical Biochemistry, 1976
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976