Molecular Oncology
Volume 3, Issue 3 , Pages 204-213, June 2009

Neurotensin signaling induces intracellular alkalinization and interleukin-8 expression in human pancreatic cancer cells

  • Ulrike Olszewski

      Affiliations

    • Department of Surgery, Medical University of Vienna, A-1090 Vienna, Austria
    • Ludwig Boltzmann Cluster of Translational Oncology, A-1010 Vienna, Austria
    • Corresponding Author InformationCorresponding author. Ludwig Boltzmann Cluster of Translational Oncology, c/o Balderichgasse 26/13, A-1170 Vienna, Austria. Tel./fax: +43 1 40400 6627.
    • ,
  • Gerhard Hamilton

      Affiliations

    • Department of Surgery, Medical University of Vienna, A-1090 Vienna, Austria
    • Ludwig Boltzmann Cluster of Translational Oncology, A-1010 Vienna, Austria

Received 15 October 2008; accepted 23 January 2009. published online 12 February 2009.

Abstract 

Pancreatic adenocarcinomas express neurotensin receptors in up to 90% of cases, however, their role in tumor biology and as a drug target is not clear. In the present study, a stable neurotensin (NT) analog induced intracellular calcium release and intracellular alkalinization in BxPC-3 and PANC-1 pancreatic cancer cells that was abolished by inhibitors of NT receptor (NTR) and sodium–proton exchanger 1 (NHE1), amiloride and SR 142948, respectively. Activation of NHE1 involved increased phosphorylation of dimethylfumarate-sensitive mitogen- and stress-activated kinase 1/2 (MSK1/2). NTR signaling appears to promote a metastatic phenotype in pancreatic cancer cells by induction of localized extracellular acidification in normoxic cells, preceeding acidosis induced by hypoxia and switch to glycolysis in addition to increased expression of interleukin-8 (IL-8).

Keywords: Pancreatic adenocarcinoma, Neurotensin, Mitogen- and stress activated kinase, Sodium hydrogen exchanger 1, Interleukin-8

Non-standard abbreviations: NT, neurotensin, NTR, neurotensin receptor, Lys8-ψ-Lys9NT(8–13), Lys8-ψ-Lys9-Pro10-Tyr11-Ile12-Leu13-OH

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PII: S1574-7891(09)00022-2

doi:10.1016/j.molonc.2009.01.006

Molecular Oncology
Volume 3, Issue 3 , Pages 204-213, June 2009

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