Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer-related deaths in United States and Europe. It is predicted that PDAC will become the second leading cause of cancer-related deaths during the next decades. The development of PDAC is not well understood, however, studies have shown that dysregulated exocrine pancreatic fluid secretion can contribute to pathologies of exocrine pancreas, including PDAC. The major roles of healthy exocrine pancreatic tissue are secretion of enzymes and bicarbonate rich fluid, where ion channels participate to fine-tune these biological processes. It is well known that ion channels located in the plasma membrane regulate multiple cellular functions and are involved in the communication between extracellular events and intracellular signaling pathways and can function as signal transducers themselves. Hereby, they contribute to maintain resting membrane potential, electrical signaling in excitable cells, and ion homeostasis. Despite their contribution to basic cellular processes, ion channels are also involved in the malignant transformation from a normal to a malignant phenotype. Aberrant expression and activity of ion channels have an impact on essentially all hallmarks of cancer defined as; uncontrolled proliferation, evasion of apoptosis, sustained angiogenesis and promotion of invasion and migration. Research indicates that certain ion channels are involved in the aberrant tumor growth and metastatic processes of PDAC. The purpose of this review is to summarize the important expression, localization, and function of ion channels in normal exocrine pancreatic tissue and how they are involved in PDAC progression and development. As ion channels are suggested to be potential targets of treatment they are furthermore suggested to be biomarkers of different cancers. Therefore, we describe the importance of ion channels in PDAC as markers of diagnosis and clinical factors.
Highlights
Ion channels are plasma membrane spanning proteins found in all human tissues, allowing rapid transport of ions and fluids between the extracellular and intracellular milieu (Niemeyer et al, 2001; Gouaux and Mackinnon, 2005)
By using mouse models associated with electrophysiological studies, Warth et al (2002) showed that KCNQ1 was predominantly located at the basolateral membrane and its co-assemblage with KCNE1 leads to a voltage-dependent K+ current that was increased by cholinergic stimulation and inhibited by the KCNQ1 blocker (Kim and Greger, 1999; Kottgen et al, 1999; Warth et al, 2002)
It might be hypothesized that the localization of store-operated channels (SOCs) and Ca2+-activated ion channels are the same in pancreatic duct cells as in acinar cells, and that they play a role in HCO3- secretion, as they play a role in enzyme and fluid secretion in acinar cells (Maleth and Hegyi, 2014)
Summary
Julie Schnipper 1, Isabelle Dhennin-Duthille 1, Ahmed Ahidouch 1,2 and Halima Ouadid-Ahidouch 1*. Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancerrelated deaths in United States and Europe. It is well known that ion channels located in the plasma membrane regulate multiple cellular functions and are involved in the communication between extracellular events and intracellular signaling pathways and can function as signal transducers themselves. Hereby, they contribute to maintain resting membrane potential, electrical signaling in excitable cells, and ion homeostasis. The purpose of this review is to summarize the important expression, localization, and function of ion channels in normal exocrine pancreatic tissue and how they are involved in PDAC progression and development.
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