Hypergravity-induced changes in actin response of breast cancer cells to natural killer cells

Abstract Although immunotherapy holds promising cytotoxic activity against lymphoma or leukemia, the immunosuppressive mechanisms of solid tumors remain challenging. In this study, we developed and applied a hypergravity exposure system as a novel strategy to improve the responsiveness of breast can...

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Autores principales:	Minseon Lee, Dongjoo Kim, Soonjo Kwon
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3ef51b61231f45e7b43f640fe3fa87f3
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spelling	oai:doaj.org-article:3ef51b61231f45e7b43f640fe3fa87f32021-12-02T13:26:28ZHypergravity-induced changes in actin response of breast cancer cells to natural killer cells10.1038/s41598-021-86799-72045-2322https://doaj.org/article/3ef51b61231f45e7b43f640fe3fa87f32021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86799-7https://doaj.org/toc/2045-2322Abstract Although immunotherapy holds promising cytotoxic activity against lymphoma or leukemia, the immunosuppressive mechanisms of solid tumors remain challenging. In this study, we developed and applied a hypergravity exposure system as a novel strategy to improve the responsiveness of breast cancer cells to natural killer (NK) cells for efficient immunotherapy. Following exposure to hypergravity, either in the presence or absence of NK cells, we investigated for changes in the cell cytoskeletal structure, which is related to the F-actin mediated immune evasion mechanism (referred to as “actin response”) of cancer cells. Breast cancer cell line MDA-MB-231 cells were exposed thrice to a 20 min hypergravitational condition (10 × g), with a 20 min rest period between each exposure. The applied hypergravity induces changes in the intracellular cytoskeleton structure without decreasing the cell viability but increasing the cytotoxicity of MDA-MB-231 from 4 to 18% (4.5-fold) at a 3:1 ratio (NK-to-target). Analyses related to F-actin further demonstrate that the applied hypergravity results in rearrangement of the cytoskeleton, leading to inhibition of the actin response of MDA-MB-231. Taken together, our results suggest that the mechanical load increases through application of hypergravity, which potentially improves efficiency of cell-based immunotherapies by sensitizing tumors to immune cell-mediated cytotoxicity.Minseon LeeDongjoo KimSoonjo KwonNature 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 Minseon Lee Dongjoo Kim Soonjo Kwon Hypergravity-induced changes in actin response of breast cancer cells to natural killer cells
description	Abstract Although immunotherapy holds promising cytotoxic activity against lymphoma or leukemia, the immunosuppressive mechanisms of solid tumors remain challenging. In this study, we developed and applied a hypergravity exposure system as a novel strategy to improve the responsiveness of breast cancer cells to natural killer (NK) cells for efficient immunotherapy. Following exposure to hypergravity, either in the presence or absence of NK cells, we investigated for changes in the cell cytoskeletal structure, which is related to the F-actin mediated immune evasion mechanism (referred to as “actin response”) of cancer cells. Breast cancer cell line MDA-MB-231 cells were exposed thrice to a 20 min hypergravitational condition (10 × g), with a 20 min rest period between each exposure. The applied hypergravity induces changes in the intracellular cytoskeleton structure without decreasing the cell viability but increasing the cytotoxicity of MDA-MB-231 from 4 to 18% (4.5-fold) at a 3:1 ratio (NK-to-target). Analyses related to F-actin further demonstrate that the applied hypergravity results in rearrangement of the cytoskeleton, leading to inhibition of the actin response of MDA-MB-231. Taken together, our results suggest that the mechanical load increases through application of hypergravity, which potentially improves efficiency of cell-based immunotherapies by sensitizing tumors to immune cell-mediated cytotoxicity.
format	article
author	Minseon Lee Dongjoo Kim Soonjo Kwon
author_facet	Minseon Lee Dongjoo Kim Soonjo Kwon
author_sort	Minseon Lee
title	Hypergravity-induced changes in actin response of breast cancer cells to natural killer cells
title_short	Hypergravity-induced changes in actin response of breast cancer cells to natural killer cells
title_full	Hypergravity-induced changes in actin response of breast cancer cells to natural killer cells
title_fullStr	Hypergravity-induced changes in actin response of breast cancer cells to natural killer cells
title_full_unstemmed	Hypergravity-induced changes in actin response of breast cancer cells to natural killer cells
title_sort	hypergravity-induced changes in actin response of breast cancer cells to natural killer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3ef51b61231f45e7b43f640fe3fa87f3
work_keys_str_mv	AT minseonlee hypergravityinducedchangesinactinresponseofbreastcancercellstonaturalkillercells AT dongjookim hypergravityinducedchangesinactinresponseofbreastcancercellstonaturalkillercells AT soonjokwon hypergravityinducedchangesinactinresponseofbreastcancercellstonaturalkillercells
_version_	1718393025185447936

Hypergravity-induced changes in actin response of breast cancer cells to natural killer cells

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