Abstract
Medulloblastoma (MB) is the most common malignant brain tumor in children and occurs mainly in the cerebellum. Important intracellular signaling molecules, such those present in the Sonic Hedgehog and Wnt pathways, are involved in its development and can also be employed to determine tumor grade and prognosis. Ectonucleotidases, particularly ecto-5′NT/CD73, are important enzymes in the malignant process of different tumor types regulating extracellular ATP and adenosine levels. Here, we investigated the activity of ectonucleotidases in three malignant human cell lines: Daoy and ONS76, being representative of primary MB, and the D283 cell line, derived from a metastatic MB. All cell lines secreted ATP into the extracellular medium while hydrolyze poorly this nucleotide, which is in agreement with the low expression and activity of pyrophosphate/phosphodiesterase, NTPDases and alkaline phosphatase. The analysis of AMP hydrolysis showed that Daoy and ONS76 completely hydrolyzed AMP, with parallel adenosine production (Daoy) and inosine accumulation (ONS76). On the other hand, D283 cell line did not hydrolyze AMP. Moreover, primary MB tumor cells, Daoy and ONS76 express the ecto-5′NT/CD73 while D283 representative of a metastatic tumor, revealed poor expression of this enzyme, while the ecto-adenosine deaminase showed higher expression in D283 compared to Daoy and ONS76 cells. Nuclear beta-catenin has been suggested as a marker for MB prognosis. Further it can promotes expression of ecto-5′NT/CD73 and suppression of adenosine deaminase. It was observed that Daoy and ONS76 showed greater nuclear beta-catenin immunoreactivity than D283, which presented mainly cytoplasmic immunoreactivity. In summary, the absence of ecto-5′NT/CD73 in the D283 cell line, a metastatic MB phenotype, suggests that high expression levels of this ectonucleotidase could be correlated with a poor prognosis in patients with MB.
Highlights
Medulloblastoma (MB) is the most common malignant brain tumor in children
We showed that variation in the ecto59NT/CD73 and adenosine deaminase (ADA) expression can be associated with correspondent b-catenin immunoreactivity levels, suggesting the importance of these enzymes as prognosis markers
Considering that E-NPPs can help to keep the ideal nucleotide levels in the extracellular medium [34] and that its expression was detected in the MB cell lines here analyzed, we evaluated the activity of these enzymes as described in Material and Methods
Summary
Medulloblastoma (MB) is the most common malignant brain tumor in children. It affects preferentially boys around 9 years of age, with few cases reporting MB among adults of over 20 years of age. MB occurs mainly in the cerebellum and posterior fossa, being able to migrate into other brain structures. This tumor generates extraneural metastasis in 7.1% of the cases, which are related to its poor prognosis [1,2]. The World Health Organization (WHO) has classified MB as a grade IV tumor, the most malignant grade [3]. This tumor is subdivided into subsets including desmoplastic/nodular, anaplastic, MB with extensive nodularity, and large cell MB [3,4]. Recent studies showed that nuclear or cytoplasmic bcatenin immunoreactivity could be related with a good or bad prognosis of patients with MB, respectively [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
