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Abstract
BackgroundEcto-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 MethodsThe 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.ResultsThe 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.ConclusionThis 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.
Highlights
Ecto-5’-nucleotidase/CD73 is expressed by various human tissues and considered the main producer of extracellular adenosine [1]
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
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 acts through A1 adenosine receptors
Summary
Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil, 2 Departamento de Bioquímica, Instituto de Ciências Básicas e da Saúde, UFRGS, Porto Alegre, RS, Brazil, 3 Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil, 4 Serviço de Patologia, Hospital de Clínicas de Porto Alegre, UFRGS, Porto Alegre, RS, Brazil, 5 Laboratório de Pesquisa em Câncer, Hospital de Clínicas de Porto Alegre, UFRGS, Porto Alegre, RS, Brazil, 6 Instituto do Câncer Infantil do RS, ICI-RS, Porto Alegre, RS, Brazil, 7 Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil, 8 Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, UFRGS, Porto Alegre, RS, Brazil, 9 Département de microbiologie-infectiologie et d’immunologie, Faculté de Médecine, Université Laval, Québec, G1V 0A6, QC, Canada, 10 Centre de recherche du CHU de Québec, Québec, G1V 4G2, QC, Canada
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