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The glycocalyx maintains a cell surface pH nanoenvironment crucial for integrin-mediated migration of human melanoma cells

  • Ion Channels, Receptors and Transporters
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Abstract

The glycocalyx consists of proteoglycans, glycoproteins, glycosaminoglycans, associated plasma proteins, and soluble glycosaminoglycans and covers the surface of all eukaryotic cells. It mediates specific recognition events, modulates biological processes such as ligand–receptor interactions, and has been proposed to affect tumor metastasis. Here, we studied whether the glycocalyx is required for melanoma cell migration. We diminished the glycocalyx of human melanoma cells by inhibiting posttranslational N-glycosylation or by enzymatic digestion of the N-glycosides. This partial destruction of the glycocalyx reduced melanoma cell migration by up to 60%. It was accompanied by the disintegration of a characteristic pH nanoenvironment typically surrounding migrating cells. Restoring this pH profile by stimulating the activity of the Na+/H+ exchanger NHE1 rescued cell migration even in the absence of an intact glycocalyx. The effects of partially removing the glycocalyx compared to those of knocking down β1-integrin expression points to a close functional correlation between glycocalyx, integrins, and cell surface pH nanoenvironment. We conclude that the glycocalyx is required for tumor cell migration. It stabilizes the cell surface pH nanoenvironment allowing a concerted pH-dependent interaction of adhesion receptors and extracellular matrix.

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Acknowledgments

This study was supported by the Deutsche Forschungsgemeinschaft (DFG; grant numbers Schw 407/10-1 and Eb 177/5-1), by the fund “Innovative Medical Research” of the University of Münster Medical School (grant number: ST 210601), and by the Rolf Dierichs-Stiftung (grant to C.S. (BD 193439)). Cariporide was a kind gift from Drs. H-J. Lang and J. Pünter at Sanofi Aventis. We extend special thanks to Drs. A. Fabian, K. Kusche-Vihrog, and Y. Treffner for technical expertise with the siRNA technique.

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Authors and Affiliations

  1. Institute of Physiology II, University of Münster, Robert-Koch-Str. 27b, 48149, Münster, Germany

    Hermann Krähling, Sabine Mally, Albrecht Schwab & Christian Stock

  2. Center of Molecular Medicine, Department of Vascular Matrix Biology, Excellence Cluster “Cardio-Pulmonary System”, University of Frankfurt, Theodor-Stern-Kai 7, Haus 9, 60590, Frankfurt am Main, Germany

    Johannes A. Eble

  3. Département de Physiologie, Université de Montréal, GÉPROM, C.P. 6128 Succ. centre-ville, Montreal, Quebec, Canada, H3C 3J7

    Josette Noël

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  1. Hermann Krähling
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Correspondence to Hermann Krähling.

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Krähling, H., Mally, S., Eble, J.A. et al. The glycocalyx maintains a cell surface pH nanoenvironment crucial for integrin-mediated migration of human melanoma cells. Pflugers Arch - Eur J Physiol 458, 1069–1083 (2009). https://doi.org/10.1007/s00424-009-0694-7

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  • DOI: https://doi.org/10.1007/s00424-009-0694-7

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