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Acidic priming enhances metastatic potential of cancer cells

  • Molecular and cellular mechanisms of disease
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Metabolic acidosis is a common feature of tumor microenvironment and may affect the phenotype of tumor cells, including invasive capacity and formation of metastases. We tested whether previous exposure to an acidic environment alters metastatic potential of two rat carcinoma cell lines in the animal model. In addition, we determined the effect of an acidic environment on motility and invasive capacity of AT-1 prostate carcinoma cells in culture. Exposure of tumor cells to an acidic environment (pH 6.6, 5 % CO2, 6 h) prior to tail vein injection in rats enhanced formation of lung metastases significantly. In culture, acidosis increased cellular motility of AT-1 cells. When the tumor cells were transferred back to pH 7.4, enhanced motility persisted for at least 3 h but vanished after longer periods (24 h), therefore presenting a “short-term memory effect.” Although acidosis augmented phosphorylation of ERK1/2 and p38, and inhibition of ERK1/2 phosphorylation or of p38 kinase activity reduced basal motility at pH 7.4, acidosis-induced increase in motility was not dependent on ERK1/2 or p38 kinase. Src family kinases were not involved either. By contrast, scavenging reactive oxygen species (ROS), known to be increased in AT-1 cells under acidic conditions, blunted acidosis-induced motility increase. Our data indicate that tumor cells may acquire enhanced motility in an acidic micromilieu, at least in part due to enhanced ROS formation. Because enhanced motility persists for at least 3 h after leaving the acidic environment, this may promote metastasis formation, as observed in our in vivo model.

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Acknowledgments

This study was supported by the Deutsche Krebshilfe (Grants 106774/106906), the BMBF (ProNet-T3 Ta-04), and the Wilhelm-Roux program of the Medical School, Universität Halle-Wittenberg.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Julius-Bernstein-Institut für Physiologie, Universität Halle-Wittenberg, Magdeburger Straße 6, 06112, Halle (Saale), Germany

    Anne Riemann, Bettina Schneider, Daniel Gündel, Oliver Thews & Michael Gekle

  2. Institute of Physiology II, University of Münster, Münster, Germany

    Christian Stock

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  1. Anne Riemann
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  2. Bettina Schneider
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  3. Daniel Gündel
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Correspondence to Anne Riemann.

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Riemann, A., Schneider, B., Gündel, D. et al. Acidic priming enhances metastatic potential of cancer cells. Pflugers Arch - Eur J Physiol 466, 2127–2138 (2014). https://doi.org/10.1007/s00424-014-1458-6

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