A 3D microvascular network model to study the impact of hypoxia on the extravasation potential of breast cell lines

© 2018, The Author(s). Hypoxia is a common feature of the tumor microenvironment. Accumulating evidence has demonstrated hypoxia to be an important trigger of tumor cell invasion or metastasizes via hypoxia-signaling cascades, including hypoxia-inducible factors (HIFs). Microfluidic model can be a r...

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Main Authors: Song, Jiho, Miermont, Agnès, Lim, Chwee Teck, Kamm, Roger D
Format: Article
Published: Springer Nature 2021
Online Access:https://hdl.handle.net/1721.1/134893
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author Song, Jiho
Miermont, Agnès
Lim, Chwee Teck
Kamm, Roger D
author_facet Song, Jiho
Miermont, Agnès
Lim, Chwee Teck
Kamm, Roger D
author_sort Song, Jiho
collection MIT
description © 2018, The Author(s). Hypoxia is a common feature of the tumor microenvironment. Accumulating evidence has demonstrated hypoxia to be an important trigger of tumor cell invasion or metastasizes via hypoxia-signaling cascades, including hypoxia-inducible factors (HIFs). Microfluidic model can be a reliable in vitro tool for systematically interrogating individual factors and their accompanying downstream effects, which may otherwise be difficult to study in complex tumor tissues. Here, we used an in vitro model of microvascular networks in a microfluidic chip to measure the extravasation potential of breast cell lines subjected to different oxygen conditions. Through the use of HIF-1α knock-down cell lines, we also validated the importance of HIF-1α in the transmigration ability of human breast cell lines. Three human breast cell lines derived from human breast tissues (MCF10A, MCF-7 and MDA-MB-231) were used in this study to evaluate the role of hypoxia in promoting metastasis at different stages of cancer progression. Under hypoxic conditions, HIF-1α protein level was increased, and coincided with changes in cell morphology, viability and an elevated metastatic potential. These changes were accompanied by an increase in the rate of extravasation compared to normoxia (21% O2). siRNA knockdown of HIF-1α in hypoxic tumors significantly decreased the extravasation rates of all the cell lines tested and may have an effect on the function of metastatic and apoptotic-related cellular processes.
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spelling mit-1721.1/1348932022-04-01T16:26:05Z A 3D microvascular network model to study the impact of hypoxia on the extravasation potential of breast cell lines Song, Jiho Miermont, Agnès Lim, Chwee Teck Kamm, Roger D © 2018, The Author(s). Hypoxia is a common feature of the tumor microenvironment. Accumulating evidence has demonstrated hypoxia to be an important trigger of tumor cell invasion or metastasizes via hypoxia-signaling cascades, including hypoxia-inducible factors (HIFs). Microfluidic model can be a reliable in vitro tool for systematically interrogating individual factors and their accompanying downstream effects, which may otherwise be difficult to study in complex tumor tissues. Here, we used an in vitro model of microvascular networks in a microfluidic chip to measure the extravasation potential of breast cell lines subjected to different oxygen conditions. Through the use of HIF-1α knock-down cell lines, we also validated the importance of HIF-1α in the transmigration ability of human breast cell lines. Three human breast cell lines derived from human breast tissues (MCF10A, MCF-7 and MDA-MB-231) were used in this study to evaluate the role of hypoxia in promoting metastasis at different stages of cancer progression. Under hypoxic conditions, HIF-1α protein level was increased, and coincided with changes in cell morphology, viability and an elevated metastatic potential. These changes were accompanied by an increase in the rate of extravasation compared to normoxia (21% O2). siRNA knockdown of HIF-1α in hypoxic tumors significantly decreased the extravasation rates of all the cell lines tested and may have an effect on the function of metastatic and apoptotic-related cellular processes. 2021-10-27T20:09:43Z 2021-10-27T20:09:43Z 2018 2019-02-15T15:22:41Z Article http://purl.org/eprint/type/JournalArticle 2045-2322 https://hdl.handle.net/1721.1/134893 Song, Jiho, Agnès Miermont, Chwee Teck Lim, and Roger D. Kamm. “A 3D Microvascular Network Model to Study the Impact of Hypoxia on the Extravasation Potential of Breast Cell Lines.” Scientific Reports 8, no. 1 (December 2018). doi:10.1038/s41598-018-36381-5. http://dx.doi.org/10.1038/s41598-018-36381-5 Scientific Reports Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Nature Scientific Reports
spellingShingle Song, Jiho
Miermont, Agnès
Lim, Chwee Teck
Kamm, Roger D
A 3D microvascular network model to study the impact of hypoxia on the extravasation potential of breast cell lines
title A 3D microvascular network model to study the impact of hypoxia on the extravasation potential of breast cell lines
title_full A 3D microvascular network model to study the impact of hypoxia on the extravasation potential of breast cell lines
title_fullStr A 3D microvascular network model to study the impact of hypoxia on the extravasation potential of breast cell lines
title_full_unstemmed A 3D microvascular network model to study the impact of hypoxia on the extravasation potential of breast cell lines
title_short A 3D microvascular network model to study the impact of hypoxia on the extravasation potential of breast cell lines
title_sort 3d microvascular network model to study the impact of hypoxia on the extravasation potential of breast cell lines
url https://hdl.handle.net/1721.1/134893
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