Abstract
The purinergic signaling has an important role in regulating pancreatic exocrine secretion. The exocrine pancreas is also a site of one of the most serious cancer forms, the pancreatic ductal adenocarcinoma (PDAC). Here, we explore how the network of purinergic and adenosine receptors, as well as ecto-nucleotidases regulate normal pancreatic cells and various cells within the pancreatic tumor microenvironment. In particular, we focus on the P2X7 receptor, P2Y2 and P2Y12 receptors, as well as A2 receptors and ecto-nucleotidases CD39 and CD73. Recent studies indicate that targeting one or more of these candidates could present new therapeutic approaches to treat pancreatic cancer. In pancreatic cancer, as much as possible of normal pancreatic function should be preserved, and therefore physiology of purinergic signaling in pancreas needs to be considered.
Highlights
Pancreatic cancer is one of the deadliest forms of cancer, and new insights into the biology of this cancer and therapeutic approaches are needed
Purinergic signaling is an integral part of exocrine pancreas physiology
Purinergic signaling components in immune cells in highly suppressive pancreatic ductal adenocarcinoma (PDAC) microenvironment have not been explored in detail yet
Summary
Pancreatic cancer is one of the deadliest forms of cancer, and new insights into the biology of this cancer and therapeutic approaches are needed. From research on other cancer forms, it is known that the latter includes nucleotides/sides interacting with purinergic receptors, various modulating enzymes and transporters that all jointly participate in purinergic signaling, as summarized in several reviews referred to below. Tumor hypoxia stimulates expression of ATP-hydrolyzing enzymes (CD39 and CD73) with a net result in increased level of adenosine, which is immunosuppressive and affecting cancer cells, as well as contributing to resistance to chemotherapy [6,7,8,9]. Purinergic signaling in pancreatic cancer is a relatively new research field and, in some instances, our knowledge needs to be supplemented with references to other cancer forms. Some promising results warrant further investigations and understanding of purinergic signaling proteins/receptors as novel therapeutic approaches to treat pancreatic cancer
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