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PLoS One ; 10(10): e0140996, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26491983

RESUMEN

BACKGROUND: Ecto-5'-nucleotidase/CD73 (ecto-5'-NT) participates in extracellular ATP catabolism by converting adenosine monophosphate (AMP) into adenosine. This enzyme affects the progression and invasiveness of different tumors. Furthermore, the expression of ecto-5'-NT has also been suggested as a favorable prognostic marker, attributing to this enzyme contradictory functions in cancer. Medulloblastoma (MB) is the most common brain tumor of the cerebellum and affects mainly children. MATERIALS AND METHODS: The effects of ecto-5'-NT overexpression on human MB tumor growth were studied in an in vivo model. Balb/c immunodeficient (nude) 6 to 14-week-old mice were used for dorsal subcutaneous xenograph tumor implant. Tumor development was evaluated by pathophysiological analysis. In addition, the expression patterns of adenosine receptors were verified. RESULTS: The human MB cell line D283, transfected with ecto-5'-NT (D283hCD73), revealed reduced tumor growth compared to the original cell line transfected with an empty vector. D283hCD73 generated tumors with a reduced proliferative index, lower vascularization, the presence of differentiated cells and increased active caspase-3 expression. Prominent A1 adenosine receptor expression rates were detected in MB cells overexpressing ecto-5'-NT. CONCLUSION: This work suggests that ecto-5'-NT promotes reduced tumor growth to reduce cell proliferation and vascularization, promote higher differentiation rates and initiate apoptosis, supposedly by accumulating adenosine, which then acts through A1 adenosine receptors. Therefore, ecto-5'-NT might be considered an important prognostic marker, being associated with good prognosis and used as a potential target for therapy.


Asunto(s)
5'-Nucleotidasa/metabolismo , Meduloblastoma/enzimología , Meduloblastoma/terapia , 5'-Nucleotidasa/genética , Adenosina Monofosfato/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular/genética , Proliferación Celular/fisiología , Humanos , Meduloblastoma/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Receptor de Adenosina A1/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
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