Ecto-5'-Nucleotidase Overexpression Reduces Tumor Growth in a Xenograph Medulloblastoma Model

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 a...

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Bibliographic Details
Published in:PloS one 2015-10, Vol.10 (10), p.e0140996-e0140996
Main Authors: Cappellari, Angélica R, Pillat, Micheli M, Souza, Hellio D N, Dietrich, Fabrícia, Oliveira, Francine H, Figueiró, Fabrício, Abujamra, Ana L, Roesler, Rafael, Lecka, Joanna, Sévigny, Jean, Battastini, Ana Maria O, Ulrich, Henning
Format: Article
Language:English
Subjects:
5'-Nucleotidase - genetics
5'-Nucleotidase - metabolism
Adenosine
Adenosine monophosphate
Adenosine Monophosphate - metabolism
AMP
Analysis
Animals
Apoptosis
Brain
Brain cancer
Brain tumors
Breast cancer
Cancer
Caspase
Caspase-3
Catabolism
CD73 antigen
Cell Line, Tumor
Cell proliferation
Cell Proliferation - genetics
Cell Proliferation - physiology
Cerebellum
Children
Enzymes
Growth
Humans
Immunodeficiency
Invasiveness
Life assessment
Medical prognosis
Medulloblastoma
Medulloblastoma - enzymology
Medulloblastoma - genetics
Medulloblastoma - therapy
Melanoma
Metastasis
Mice
Mice, Inbred BALB C
Mice, Nude
Nucleotidase
Nucleotidases
Pediatrics
Prognosis
Receptor, Adenosine A1 - metabolism
Receptors
Surgical implants
Tumors
Vascularization
Xenograft Model Antitumor Assays
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Summary: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. 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. 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. 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0140996