Cargando…
Extracellular protonation modulates cell-cell interaction mechanics and tissue invasion in human melanoma cells
Detachment of cells from the primary tumour precedes metastatic progression by facilitating cell release into the tissue. Solid tumours exhibit altered pH homeostasis with extracellular acidification. In human melanoma, the Na(+)/H(+) exchanger NHE1 is an important modifier of the tumour nanoenviron...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5304230/ https://www.ncbi.nlm.nih.gov/pubmed/28205573 http://dx.doi.org/10.1038/srep42369 |
_version_ | 1782506852088545280 |
---|---|
author | Hofschröer, Verena Koch, Alexander Ludwig, Florian Timo Friedl, Peter Oberleithner, Hans Stock, Christian Schwab, Albrecht |
author_facet | Hofschröer, Verena Koch, Alexander Ludwig, Florian Timo Friedl, Peter Oberleithner, Hans Stock, Christian Schwab, Albrecht |
author_sort | Hofschröer, Verena |
collection | PubMed |
description | Detachment of cells from the primary tumour precedes metastatic progression by facilitating cell release into the tissue. Solid tumours exhibit altered pH homeostasis with extracellular acidification. In human melanoma, the Na(+)/H(+) exchanger NHE1 is an important modifier of the tumour nanoenvironment. Here we tested the modulation of cell-cell-adhesion by extracellular pH and NHE1. MV3 tumour spheroids embedded in a collagen matrix unravelled the efficacy of cell-cell contact loosening and 3D emigration into an environment mimicking physiological confinement. Adhesive interaction strength between individual MV3 cells was quantified using atomic force microscopy and validated by multicellular aggregation assays. Extracellular acidification from pH(e)7.4 to 6.4 decreases cell migration and invasion but increases single cell detachment from the spheroids. Acidification and NHE1 overexpression both reduce cell-cell adhesion strength, indicated by reduced maximum pulling forces and adhesion energies. Multicellular aggregation and spheroid formation are strongly impaired under acidification or NHE1 overexpression. We show a clear dependence of melanoma cell-cell adhesion on pH(e) and NHE1 as a modulator. These effects are opposite to cell-matrix interactions that are strengthened by protons extruded via NHE1. We conclude that these opposite effects of NHE1 act synergistically during the metastatic cascade. |
format | Online Article Text |
id | pubmed-5304230 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53042302017-03-14 Extracellular protonation modulates cell-cell interaction mechanics and tissue invasion in human melanoma cells Hofschröer, Verena Koch, Alexander Ludwig, Florian Timo Friedl, Peter Oberleithner, Hans Stock, Christian Schwab, Albrecht Sci Rep Article Detachment of cells from the primary tumour precedes metastatic progression by facilitating cell release into the tissue. Solid tumours exhibit altered pH homeostasis with extracellular acidification. In human melanoma, the Na(+)/H(+) exchanger NHE1 is an important modifier of the tumour nanoenvironment. Here we tested the modulation of cell-cell-adhesion by extracellular pH and NHE1. MV3 tumour spheroids embedded in a collagen matrix unravelled the efficacy of cell-cell contact loosening and 3D emigration into an environment mimicking physiological confinement. Adhesive interaction strength between individual MV3 cells was quantified using atomic force microscopy and validated by multicellular aggregation assays. Extracellular acidification from pH(e)7.4 to 6.4 decreases cell migration and invasion but increases single cell detachment from the spheroids. Acidification and NHE1 overexpression both reduce cell-cell adhesion strength, indicated by reduced maximum pulling forces and adhesion energies. Multicellular aggregation and spheroid formation are strongly impaired under acidification or NHE1 overexpression. We show a clear dependence of melanoma cell-cell adhesion on pH(e) and NHE1 as a modulator. These effects are opposite to cell-matrix interactions that are strengthened by protons extruded via NHE1. We conclude that these opposite effects of NHE1 act synergistically during the metastatic cascade. Nature Publishing Group 2017-02-13 /pmc/articles/PMC5304230/ /pubmed/28205573 http://dx.doi.org/10.1038/srep42369 Text en Copyright © 2017, The Author(s) https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) |
spellingShingle | Article Hofschröer, Verena Koch, Alexander Ludwig, Florian Timo Friedl, Peter Oberleithner, Hans Stock, Christian Schwab, Albrecht Extracellular protonation modulates cell-cell interaction mechanics and tissue invasion in human melanoma cells |
title | Extracellular protonation modulates cell-cell interaction mechanics and tissue invasion
in human melanoma cells |
title_full | Extracellular protonation modulates cell-cell interaction mechanics and tissue invasion
in human melanoma cells |
title_fullStr | Extracellular protonation modulates cell-cell interaction mechanics and tissue invasion
in human melanoma cells |
title_full_unstemmed | Extracellular protonation modulates cell-cell interaction mechanics and tissue invasion
in human melanoma cells |
title_short | Extracellular protonation modulates cell-cell interaction mechanics and tissue invasion
in human melanoma cells |
title_sort | extracellular protonation modulates cell-cell interaction mechanics and tissue invasion
in human melanoma cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5304230/ https://www.ncbi.nlm.nih.gov/pubmed/28205573 http://dx.doi.org/10.1038/srep42369 |
work_keys_str_mv | AT hofschroerverena extracellularprotonationmodulatescellcellinteractionmechanicsandtissueinvasioninhumanmelanomacells AT kochalexander extracellularprotonationmodulatescellcellinteractionmechanicsandtissueinvasioninhumanmelanomacells AT ludwigfloriantimo extracellularprotonationmodulatescellcellinteractionmechanicsandtissueinvasioninhumanmelanomacells AT friedlpeter extracellularprotonationmodulatescellcellinteractionmechanicsandtissueinvasioninhumanmelanomacells AT oberleithnerhans extracellularprotonationmodulatescellcellinteractionmechanicsandtissueinvasioninhumanmelanomacells AT stockchristian extracellularprotonationmodulatescellcellinteractionmechanicsandtissueinvasioninhumanmelanomacells AT schwabalbrecht extracellularprotonationmodulatescellcellinteractionmechanicsandtissueinvasioninhumanmelanomacells |