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

• 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
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0140996

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.