Characterizing the effect of substrate stiffness on the extravasation potential of breast cancer cells using a 3D microfluidic model.

Azadi, S; Tafazzoli Shadpour, M; Warkiani, ME

Characterizing the effect of substrate stiffness on the extravasation potential of breast cancer cells using a 3D microfluidic model.

Azadi, S Tafazzoli Shadpour, M Warkiani, ME

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Publisher:: Wiley
Publication Type:: Journal Article
Citation:: Biotechnology and Bioengineering, 2021, 118, (2), pp. 823-835
Issue Date:: 2021-02

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Field	Value	Language
dc.contributor.author	Azadi, S
dc.contributor.author	Tafazzoli Shadpour, M
dc.contributor.author	Warkiani, ME
dc.date.accessioned	2022-03-08T04:14:23Z
dc.date.available	2020-10-20
dc.date.available	2022-03-08T04:14:23Z
dc.date.issued	2021-02
dc.identifier.citation	Biotechnology and Bioengineering, 2021, 118, (2), pp. 823-835
dc.identifier.issn	0006-3592
dc.identifier.issn	1097-0290
dc.identifier.uri	http://hdl.handle.net/10453/155055
dc.description.abstract	Different biochemical and biomechanical cues from tumor microenvironment affect the extravasation of cancer cells to distant organs; among them, the mechanical signals are poorly understood. Although the effect of substrate stiffness on the primary migration of cancer cells has been previously probed, its role in regulating the extravasation ability of cancer cells is still vague. Herein, we used a microfluidic device to mimic the extravasation of tumor cells in a 3D microenvironment containing cancer cells, endothelial cells, and the biological matrix. The microfluidic-based extravasation model was utilized to probe the effect of substrate stiffness on the invasion ability of breast cancer cells. MCF7 and MDA-MB-231 cancer cells were cultured among substrates with different stiffness which followed by monitoring their extravasation capability through the microfluidic device. Our results demonstrated that acidic collagen at a concentration of 2.5 mg/ml promotes migration of cancer cells. Additionally, the substrate softening resulted in up to 46% reduction in the invasion of breast cancer cells. The substrate softening not only affected the number of extravasated cells but also reduced their migration distance up to 53%. We further investigated the secreted level of matrix metalloproteinase 9 (MMP9) and identified that there is a positive correlation between substrate stiffening, MMP9 concentration, and extravasation of cancer cells. These findings suggest that the substrate stiffness mediates the cancer cells extravasation in a microfluidic model. Changes in MMP9 level could be one of the possible underlying mechanisms which need more investigations to be addressed thoroughly.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Wiley
dc.relation.ispartof	Biotechnology and Bioengineering
dc.relation.isbasedon	10.1002/bit.27612
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject.classification	Biotechnology
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Cell Movement
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	MCF-7 Cells
dc.subject.mesh	Microfluidic Analytical Techniques
dc.subject.mesh	Models, Biological
dc.subject.mesh	Neoplasm Invasiveness
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Cell Movement
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	MCF-7 Cells
dc.subject.mesh	Microfluidic Analytical Techniques
dc.subject.mesh	Models, Biological
dc.subject.mesh	Neoplasm Invasiveness
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Humans
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Neoplasm Invasiveness
dc.subject.mesh	Microfluidic Analytical Techniques
dc.subject.mesh	Cell Movement
dc.subject.mesh	Models, Biological
dc.subject.mesh	Female
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	MCF-7 Cells
dc.title	Characterizing the effect of substrate stiffness on the extravasation potential of breast cancer cells using a 3D microfluidic model.
dc.type	Journal Article
utslib.citation.volume	118
utslib.location.activity	United States
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	recently_added	*
pubs.consider-herdc	false
dc.date.updated	2022-03-08T04:14:18Z
pubs.issue	2
pubs.publication-status	Published
pubs.volume	118
utslib.citation.issue	2

Abstract:

Different biochemical and biomechanical cues from tumor microenvironment affect the extravasation of cancer cells to distant organs; among them, the mechanical signals are poorly understood. Although the effect of substrate stiffness on the primary migration of cancer cells has been previously probed, its role in regulating the extravasation ability of cancer cells is still vague. Herein, we used a microfluidic device to mimic the extravasation of tumor cells in a 3D microenvironment containing cancer cells, endothelial cells, and the biological matrix. The microfluidic-based extravasation model was utilized to probe the effect of substrate stiffness on the invasion ability of breast cancer cells. MCF7 and MDA-MB-231 cancer cells were cultured among substrates with different stiffness which followed by monitoring their extravasation capability through the microfluidic device. Our results demonstrated that acidic collagen at a concentration of 2.5 mg/ml promotes migration of cancer cells. Additionally, the substrate softening resulted in up to 46% reduction in the invasion of breast cancer cells. The substrate softening not only affected the number of extravasated cells but also reduced their migration distance up to 53%. We further investigated the secreted level of matrix metalloproteinase 9 (MMP9) and identified that there is a positive correlation between substrate stiffening, MMP9 concentration, and extravasation of cancer cells. These findings suggest that the substrate stiffness mediates the cancer cells extravasation in a microfluidic model. Changes in MMP9 level could be one of the possible underlying mechanisms which need more investigations to be addressed thoroughly.

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http://hdl.handle.net/10453/155055