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The effect of mechanosensitive channel MscL expression in cancer cells on 3D confined migration

Metastatic cancer cells migrate through constricted spaces and experience significant compressive stress, but mechanisms enabling migration in confined geometries remain unclear. Cancer cell migration within confined 3-dimensional (3D) microfluidic channels has been shown to be distinct from 2D cell...

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Autores principales: Heureaux-Torres, Johanna, Luker, Kathryn E., Haley, Henry, Pirone, Matthew, Lee, Lap Man, Herrera, Yoani, Luker, Gary D., Liu, Allen P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AIP Publishing LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324216/
https://www.ncbi.nlm.nih.gov/pubmed/31069318
http://dx.doi.org/10.1063/1.5019770
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author Heureaux-Torres, Johanna
Luker, Kathryn E.
Haley, Henry
Pirone, Matthew
Lee, Lap Man
Herrera, Yoani
Luker, Gary D.
Liu, Allen P.
author_facet Heureaux-Torres, Johanna
Luker, Kathryn E.
Haley, Henry
Pirone, Matthew
Lee, Lap Man
Herrera, Yoani
Luker, Gary D.
Liu, Allen P.
author_sort Heureaux-Torres, Johanna
collection PubMed
description Metastatic cancer cells migrate through constricted spaces and experience significant compressive stress, but mechanisms enabling migration in confined geometries remain unclear. Cancer cell migration within confined 3-dimensional (3D) microfluidic channels has been shown to be distinct from 2D cell migration. However, whether 3D confined migration can be manipulated by mechanosensory components has not been examined in detail. In this work, we exogenously introduced a mechanosensitive channel of large conductance (MscL) into metastatic breast cancer cells MDA-MB-231. We discovered that inducing expression of a gain-of-function G22S mutant of MscL in MDA-MB-231 cells significantly reduced spontaneous lung metastasis without affecting the growth of orthotopic tumor implants. To further investigate the effects of G22S MscL on cell migration, we designed a microfluidic device with channels of various cross-sections ranging from a 2D planar environment to narrow 3D constrictions. Both MscL G22S and control breast cancer cells migrated progressively slower in more constricted environments. Migration of cells expressing MscL G22S did not differ from control cells, even though MscL was activated in cells in constricted channels of 3 μm width. Interestingly, we found MscL expressing cells to be more frequently “stuck” at the entrance of the 3 μm channels and failed to migrate into the microchannel. Our work demonstrates the possibility of engineering mechanotransduction for controlling confined cell migration.
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spelling pubmed-63242162019-05-08 The effect of mechanosensitive channel MscL expression in cancer cells on 3D confined migration Heureaux-Torres, Johanna Luker, Kathryn E. Haley, Henry Pirone, Matthew Lee, Lap Man Herrera, Yoani Luker, Gary D. Liu, Allen P. APL Bioeng Special Topic: Bioengineering of Cancer Metastatic cancer cells migrate through constricted spaces and experience significant compressive stress, but mechanisms enabling migration in confined geometries remain unclear. Cancer cell migration within confined 3-dimensional (3D) microfluidic channels has been shown to be distinct from 2D cell migration. However, whether 3D confined migration can be manipulated by mechanosensory components has not been examined in detail. In this work, we exogenously introduced a mechanosensitive channel of large conductance (MscL) into metastatic breast cancer cells MDA-MB-231. We discovered that inducing expression of a gain-of-function G22S mutant of MscL in MDA-MB-231 cells significantly reduced spontaneous lung metastasis without affecting the growth of orthotopic tumor implants. To further investigate the effects of G22S MscL on cell migration, we designed a microfluidic device with channels of various cross-sections ranging from a 2D planar environment to narrow 3D constrictions. Both MscL G22S and control breast cancer cells migrated progressively slower in more constricted environments. Migration of cells expressing MscL G22S did not differ from control cells, even though MscL was activated in cells in constricted channels of 3 μm width. Interestingly, we found MscL expressing cells to be more frequently “stuck” at the entrance of the 3 μm channels and failed to migrate into the microchannel. Our work demonstrates the possibility of engineering mechanotransduction for controlling confined cell migration. AIP Publishing LLC 2018-06-08 /pmc/articles/PMC6324216/ /pubmed/31069318 http://dx.doi.org/10.1063/1.5019770 Text en © 2018 Author(s). 2473-2877/2018/2(3)/032001/12 All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Special Topic: Bioengineering of Cancer
Heureaux-Torres, Johanna
Luker, Kathryn E.
Haley, Henry
Pirone, Matthew
Lee, Lap Man
Herrera, Yoani
Luker, Gary D.
Liu, Allen P.
The effect of mechanosensitive channel MscL expression in cancer cells on 3D confined migration
title The effect of mechanosensitive channel MscL expression in cancer cells on 3D confined migration
title_full The effect of mechanosensitive channel MscL expression in cancer cells on 3D confined migration
title_fullStr The effect of mechanosensitive channel MscL expression in cancer cells on 3D confined migration
title_full_unstemmed The effect of mechanosensitive channel MscL expression in cancer cells on 3D confined migration
title_short The effect of mechanosensitive channel MscL expression in cancer cells on 3D confined migration
title_sort effect of mechanosensitive channel mscl expression in cancer cells on 3d confined migration
topic Special Topic: Bioengineering of Cancer
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324216/
https://www.ncbi.nlm.nih.gov/pubmed/31069318
http://dx.doi.org/10.1063/1.5019770
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