Oncotarget

Research Papers:

Ion channels in control of pancreatic stellate cell migration

Hannah Storck, Benedikt Hild, Sandra Schimmelpfennig, Sarah Sargin, Nikolaj Nielsen, Angela Zaccagnino, Thomas Budde, Ivana Novak, Holger Kalthoff and Albrecht Schwab _

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Oncotarget. 2017; 8:769-784. https://doi.org/10.18632/oncotarget.13647

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Abstract

Hannah Storck1, Benedikt Hild1, Sandra Schimmelpfennig1, Sarah Sargin1, Nikolaj Nielsen1, Angela Zaccagnino4, Thomas Budde2, Ivana Novak3, Holger Kalthoff4, Albrecht Schwab1

1Institut für Physiologie II, 48149 Münster, Gemany

2Institut für Physiologie I, 48149 Münster, Gemany

3Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, DK 2100 Copenhagen, Denmark

4UKSH, Campus Kiel, Institut für Experimentelle Tumorforschung (IET), Sektion Molekulare Onkologie, D-24105 Kiel, Germany

Correspondence to:

Albrecht Schwab, email: [email protected]

Keywords: pancreatic stellate cell, migration, KCa3.1 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 KCa3.1 channels in PSCs. KCa3.1 channels are also found in many tumor cells of different origin. We revealed the functional expression of KCa3.1 channels by means of Western blot, immunofluorescence and patch clamp analysis. The impact of KCa3.1 channel activity on PSC function was determined with live-cell imaging and by measuring the intracellular Ca2+ concentration ([Ca2+]i). KCa3.1 channel blockade or knockout prevents the stimulation of PSC migration and chemotaxis by reducing the [Ca2+]i and calpain activity. KCa3.1 channels functionally cooperate with TRPC3 channels that are upregulated in PDAC stroma. Knockdown of TRPC3 channels largely abolishes the impact of KCa3.1 channels on PSC migration. In summary, our results clearly show that ion channels are crucial players in PSC physiology and pathophysiology.


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