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Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice
Published on: December 21, 2019
P2X7 targeting inhibits growth of human mesothelioma
Francesca Amoroso1, Erica Salaro1, Simonetta Falzoni1
1Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
Abstract:
Malignant pleural mesothelioma (MPM) is an aggressive tumor refractory to anti-blastic therapy. MPM cells show several genetic and biochemical defects, e.g. overexpression of oncogenes, downregulation of onco-suppressor genes, dysregulation of microRNA, or alteration of intracellular Ca2+ homeostasis and of apoptosis. No information is as yet available on purinergic signalling in this tumor. Signalling via the P2X7 (P2RX7 or P2X7R) purinergic receptor is attracting increasing attention as a pathway involved in cancer cell death or proliferation. In this report we show that the P2X7R is expressed by three MPM cell lines established from MPM patients but not by mesothelial cells from healthy subjects (healthy mesothelial cells, HMCs). MPM cell proliferation was inhibited by in vitro incubation in the presence of selective P2X7R antagonists, as well as by stimulation with the P2X7R agonist BzATP. Systemic administration of the selective P2X7R blocker AZ10606120 inhibited in vivo growth of MPM tumors whether implanted subcutaneously (s.c.) or intraperitoneally (i.p.). Our findings suggest that the P2X7R might be a novel target for the therapy of mesothelioma.
Insights
The P2X7 receptor (P2X7R) is expressed in malignant pleural mesothelioma (MPM) cells, unlike in healthy cells. Blocking P2X7R inhibits tumor growth, suggesting it as a new therapeutic target for mesothelioma.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options.
- MPM cells exhibit various genetic and biochemical abnormalities, but purinergic signaling in MPM is unexplored.
- The P2X7 receptor (P2X7R) is implicated in cancer cell proliferation and death.
Purpose of the Study:
- To investigate the role of P2X7R in malignant pleural mesothelioma.
- To determine if P2X7R is a potential therapeutic target for MPM.
Main Methods:
- Expression analysis of P2X7R in MPM cell lines and healthy mesothelial cells.
- In vitro assessment of MPM cell proliferation using P2X7R antagonists and agonists.
- In vivo evaluation of P2X7R blocker AZ10606120 on subcutaneous and intraperitoneal MPM tumor growth.
Main Results:
- P2X7R was expressed in MPM cell lines but not in healthy mesothelial cells.
- In vitro incubation with P2X7R antagonists or agonists inhibited MPM cell proliferation.
- Systemic administration of the P2X7R blocker AZ10606120 suppressed in vivo MPM tumor growth.
Conclusions:
- P2X7R is present in malignant pleural mesothelioma cells.
- P2X7R signaling influences MPM cell proliferation and tumor growth.
- P2X7R represents a promising novel therapeutic target for mesothelioma treatment.
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