Overexpression of NTPDase2 in gliomas promotes systemic inflammation and pulmonary injury

Elizandra Braganhol, Rafael F. Zanin, Andressa Bernardi, Leticia S. Bergamin, Angelica R. Cappellari, Luis F. Campesato, Fernanda B. Morrone, Maria M. Campos, João B. Calixto, Maria Isabel A Edelweiss, Márcia R. Wink, Jean Sévigny, Simon C. Robson, Ana Maria O Battastini

Research output: Contribution to journalArticlepeer-review

Abstract

Gliomas are the most common and devastating type of primary brain tumor. Many non-neoplastic cells, including immune cells, comprise the tumor microenvironment where they create a milieu that appears to dictate cancer development. ATP and the phosphohydrolytic products ADP and adenosine by activating P2 and P1 receptors may participate in these interactions among malignant and immune cells. Purinergic receptor-mediated cell communication is closely regulated by ectonucleotidases, such as by members of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family, which hydrolyze extracellular nucleotides. We have shown that gliomas, unlike astrocytes, exhibit low NTPDase activity. Furthermore, ATP induces glioma cell proliferation and the co-administration of apyrase decreases progression of injected cells in vivo. We have previously shown that NTPDase2 reconstitution dramatically increases tumor growth in vivo. Here we evaluated whether NTPDase2 reconstitution to gliomas modulates systemic inflammatory responses. We observed that NTPDase2 overexpression modulated pro-inflammatory cytokine production and platelet reactivity. Additionally, pathological alterations in the lungs were observed in rats bearing these tumors. Our results suggest that disruption of purinergic signaling via ADP accumulation creates an inflammatory state that may promote tumor spread and dictate clinical progression.

Original languageEnglish
Pages (from-to)235-243
Number of pages9
JournalPurinergic Signalling
Volume8
Issue number2
DOIs
Publication statusPublished - Jun 2012

Keywords

  • ADP
  • ATP
  • E-NTPDases
  • Gliomas
  • Inflammation
  • Lung

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Overexpression of NTPDase2 in gliomas promotes systemic inflammation and pulmonary injury'. Together they form a unique fingerprint.

Cite this