title: The glycocalyx maintains a cell surface pH nanoenvironment crucial for integrin-mediated migration of human melanoma cells.
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 beta(1)-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.
authors: Institute of Physiology II, University of Münster, Robert-Koch-Str. 27b, 48149, Münster, Germany. lordon.green@gmx.de
authors: Hermann
authors: H
authors: Krähling
authors: Sabine
authors: S
authors: Mally
authors: Johannes A
authors: JA
authors: Eble
authors: Josette
authors: J
authors: Noël
authors: Albrecht
authors: A
authors: Schwab
authors: Christian
authors: C
authors: Stock
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D055785:Gene Knockdown Techniques; D019276:Glycocalyx / Q000502:physiology*; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D038982:Integrin alpha2beta1 / Q000037:antagonists & inhibitors; D019012:Integrin beta1 / Q000096:biosynthesis; D016023:Integrins / Q000502:physiology; D008545:Melanoma / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D027682:Cation Transport Proteins; D038982:Integrin alpha2beta1; D019012:Integrin beta1; D016023:Integrins; D034741:RNA, Small Interfering; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D014415:Tunicamycin