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- W2556038631 abstract "// Hannah Storck 1 , Benedikt Hild 1 , Sandra Schimmelpfennig 1 , Sarah Sargin 1 , Nikolaj Nielsen 1 , Angela Zaccagnino 4 , Thomas Budde 2 , Ivana Novak 3 , Holger Kalthoff 4 , Albrecht Schwab 1 1 Institut für Physiologie II, 48149 Münster, Gemany 2 Institut für Physiologie I, 48149 Münster, Gemany 3 Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, DK 2100 Copenhagen, Denmark 4 UKSH, Campus Kiel, Institut für Experimentelle Tumorforschung (IET), Sektion Molekulare Onkologie, D-24105 Kiel, Germany Correspondence to: Albrecht Schwab, email: aschwab@uni-muenster.de Keywords: pancreatic stellate cell, migration, K Ca 3.1 channel, TRPC3 channel Received: August 25, 2016 Accepted: November 07, 2016 Published: November 26, 2016 ABSTRACT Pancreatic stellate cells (PSCs) play a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC). Once activated, PSCs support proliferation and metastasis of carcinoma cells. PSCs even co-metastasise with carcinoma cells. This requires the ability of PSCs to migrate. In recent years, it has been established that almost all “hallmarks of cancer” such as proliferation or migration/invasion also rely on the expression and function of ion channels. So far, there is only very limited information about the function of ion channels in PSCs. Yet, there is growing evidence that ion channels in stromal cells also contribute to tumor progression. Here we investigated the function of K Ca 3.1 channels in PSCs. K Ca 3.1 channels are also found in many tumor cells of different origin. We revealed the functional expression of K Ca 3.1 channels by means of Western blot, immunofluorescence and patch clamp analysis. The impact of K Ca 3.1 channel activity on PSC function was determined with live-cell imaging and by measuring the intracellular Ca2 + concentration ([Ca 2+ ] i ). K Ca 3.1 channel blockade or knockout prevents the stimulation of PSC migration and chemotaxis by reducing the [Ca 2+ ] i and calpain activity. K Ca 3.1 channels functionally cooperate with TRPC3 channels that are upregulated in PDAC stroma. Knockdown of TRPC3 channels largely abolishes the impact of K Ca 3.1 channels on PSC migration. In summary, our results clearly show that ion channels are crucial players in PSC physiology and pathophysiology." @default.
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- W2556038631 date "2016-11-26" @default.
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- W2556038631 title "Ion channels in control of pancreatic stellate cell migration" @default.
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- W2556038631 doi "https://doi.org/10.18632/oncotarget.13647" @default.
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