The context-dependent role of the Na+/Ca2+-exchanger (NCX) in pancreatic stellate cell migration

• DOI: 10.1007/s00424-023-02847-3
• Publication Date: 2023-08-11T12:03:11Z
• Authors: Thorsten Loeck; Micol Rugi; Luca Matteo Todesca; Paulina Kalinowska; Benjamin Soret; Ilka Neumann; Sandra Schimmelpf...; Karolina Najder; Zoltán Pethő; Valerio Farfariello; Natalia Prevarskaya; Albrecht Schwab
• Keywords: Sodium-calcium exchanger; Homeostasis; Hepatic stellate cell

Abstract Pancreatic stellate cells (PSCs) that can co-metastasize with cancer shape the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) by producing an excessive amount of extracellular matrix. This leads to a TME characterized increased tissue pressure, hypoxia, and acidity. Moreover, within secrete growth factors. The stimuli trigger Ca 2+ signaling cellular Na + loading. /Ca exchanger (NCX) connects homeostasis. NCX is electrogenic transporter, which shuffles 1 against 3 ions over plasma membrane forward or reverse mode. Here, we studied how impact activity on PSC migration modulated cues from TME. expression was revealed qPCR Western blot. [Ca ] i , [Na cell potential were determined fluorescent indicators Fura-2, Asante NaTRIUM Green-2, DiBAC 4 (3), respectively. quantified live-cell imaging. To mimic TME, PSCs exposed acidic pH (pH 6.6), PDGF. NCX-dependent blot analyses. express NCX1.3 NCX1.9. are 94.4 nmol/l, 7.4 mmol/l, − 39.8 mV, Thus, NCX1 usually operates (Ca export) plays differential role translating into altered migratory behavior. When operating mode, its inhibition accelerates migration. NCX1-mediated extrusion contributes slow mode PSCs.