Melanoma cells adopt features of both mesenchymal and amoeboid migration within confining channels

Abstract For metastasis to occur, cancer cells must traverse a range of tissue environments. In part, this is accomplished by cells adjusting their migration mode to one that is best suited to the environment. Melanoma cells have been shown to be particularly plastic, frequently using both mesenchym...

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Autores principales:	Sairisheel R. Gabbireddy, Karl W. Vosatka, Aram J Chung, Jeremy S. Logue
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a66ff8a03c3642bd9c7c9e83633e3afe
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spelling	oai:doaj.org-article:a66ff8a03c3642bd9c7c9e83633e3afe2021-12-02T17:19:14ZMelanoma cells adopt features of both mesenchymal and amoeboid migration within confining channels10.1038/s41598-021-97348-72045-2322https://doaj.org/article/a66ff8a03c3642bd9c7c9e83633e3afe2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97348-7https://doaj.org/toc/2045-2322Abstract For metastasis to occur, cancer cells must traverse a range of tissue environments. In part, this is accomplished by cells adjusting their migration mode to one that is best suited to the environment. Melanoma cells have been shown to be particularly plastic, frequently using both mesenchymal and amoeboid (bleb-based) modes of migration. It has been demonstrated that 2D confinement will promote the transition from mesenchymal to bleb-based migration. However, if melanoma cells similarly transition to bleb-based migration in response to 3D confinement, such as within narrow channels, is unknown. Here, using micro-fabricated channels, we demonstrate that metastatic, A375-M2, melanoma cells adopt features of both mesenchymal and bleb-based migration. In narrow (8 µm; height and width) channels coated with fibronectin, ~ 50% of melanoma cells were found to use either mesenchymal or bleb-based migration modes. In contrast, the inhibition of Src family kinases or coating channels with BSA, completely eliminated any features of mesenchymal migration. Detailed comparisons of migration parameters revealed that blebbing cells, particularly in the absence of adhesions, were faster than mesenchymal cells. In contrast to what has been previously shown under conditions of 2D confinement, pharmacologically inhibiting Arp2/3 promoted a fast filopodial-based mode of migration. Accordingly, we report that melanoma cells adopt a unique range of phenotypes under conditions of 3D confinement.Sairisheel R. GabbireddyKarl W. VosatkaAram J ChungJeremy S. LogueNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sairisheel R. Gabbireddy Karl W. Vosatka Aram J Chung Jeremy S. Logue Melanoma cells adopt features of both mesenchymal and amoeboid migration within confining channels
description	Abstract For metastasis to occur, cancer cells must traverse a range of tissue environments. In part, this is accomplished by cells adjusting their migration mode to one that is best suited to the environment. Melanoma cells have been shown to be particularly plastic, frequently using both mesenchymal and amoeboid (bleb-based) modes of migration. It has been demonstrated that 2D confinement will promote the transition from mesenchymal to bleb-based migration. However, if melanoma cells similarly transition to bleb-based migration in response to 3D confinement, such as within narrow channels, is unknown. Here, using micro-fabricated channels, we demonstrate that metastatic, A375-M2, melanoma cells adopt features of both mesenchymal and bleb-based migration. In narrow (8 µm; height and width) channels coated with fibronectin, ~ 50% of melanoma cells were found to use either mesenchymal or bleb-based migration modes. In contrast, the inhibition of Src family kinases or coating channels with BSA, completely eliminated any features of mesenchymal migration. Detailed comparisons of migration parameters revealed that blebbing cells, particularly in the absence of adhesions, were faster than mesenchymal cells. In contrast to what has been previously shown under conditions of 2D confinement, pharmacologically inhibiting Arp2/3 promoted a fast filopodial-based mode of migration. Accordingly, we report that melanoma cells adopt a unique range of phenotypes under conditions of 3D confinement.
format	article
author	Sairisheel R. Gabbireddy Karl W. Vosatka Aram J Chung Jeremy S. Logue
author_facet	Sairisheel R. Gabbireddy Karl W. Vosatka Aram J Chung Jeremy S. Logue
author_sort	Sairisheel R. Gabbireddy
title	Melanoma cells adopt features of both mesenchymal and amoeboid migration within confining channels
title_short	Melanoma cells adopt features of both mesenchymal and amoeboid migration within confining channels
title_full	Melanoma cells adopt features of both mesenchymal and amoeboid migration within confining channels
title_fullStr	Melanoma cells adopt features of both mesenchymal and amoeboid migration within confining channels
title_full_unstemmed	Melanoma cells adopt features of both mesenchymal and amoeboid migration within confining channels
title_sort	melanoma cells adopt features of both mesenchymal and amoeboid migration within confining channels
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a66ff8a03c3642bd9c7c9e83633e3afe
work_keys_str_mv	AT sairisheelrgabbireddy melanomacellsadoptfeaturesofbothmesenchymalandamoeboidmigrationwithinconfiningchannels AT karlwvosatka melanomacellsadoptfeaturesofbothmesenchymalandamoeboidmigrationwithinconfiningchannels AT aramjchung melanomacellsadoptfeaturesofbothmesenchymalandamoeboidmigrationwithinconfiningchannels AT jeremyslogue melanomacellsadoptfeaturesofbothmesenchymalandamoeboidmigrationwithinconfiningchannels
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Melanoma cells adopt features of both mesenchymal and amoeboid migration within confining channels

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