UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Cancer cells grown in 3D under fluid flow exhibit an aggressive phenotype and reduced responsiveness to the anti-cancer treatment doxorubicin

Azimi, T; Loizidou, M; Dwek, MV; (2020) Cancer cells grown in 3D under fluid flow exhibit an aggressive phenotype and reduced responsiveness to the anti-cancer treatment doxorubicin. Scientific Reports , 10 , Article 12020. 10.1038/s41598-020-68999-9. Green open access

[thumbnail of Azimi_et_al-2020-Scientific_Reports.pdf]
Preview
Text
Azimi_et_al-2020-Scientific_Reports.pdf - Published version

Download (1MB) | Preview

Abstract

3D laboratory models of cancer are designed to recapitulate the biochemical and biophysical characteristics of the tumour microenvironment and aim to enable studies of cancer, and new therapeutic modalities, in a physiologically-relevant manner. We have developed an in vitro 3D model comprising a central high-density mass of breast cancer cells surrounded by collagen type-1 and we incorporated fluid flow and pressure. We noted significant changes in cancer cell behaviour using this system. MDA-MB231 and SKBR3 breast cancer cells grown in 3D downregulated the proliferative marker Ki67 (P < 0.05) and exhibited decreased response to the chemotherapeutic agent doxorubicin (DOX) (P < 0.01). Mesenchymal markers snail and MMP14 were upregulated in cancer cells maintained in 3D (P < 0.001), cadherin-11 was downregulated (P < 0.001) and HER2 increased (P < 0.05). Cells maintained in 3D under fluid flow exhibited a further reduction in response to DOX (P < 0.05); HER2 and Ki67 levels were also attenuated. Fluid flow and pressure was associated with reduced cell viability and decreased expression levels of vimentin. In summary, aggressive cancer cell behaviour and reduced drug responsiveness was observed when breast cancer cells were maintained in 3D under fluid flow and pressure. These observations are relevant for future developments of 3D in vitro cancer models and organ-on-a-chip initiatives.

Type: Article
Title: Cancer cells grown in 3D under fluid flow exhibit an aggressive phenotype and reduced responsiveness to the anti-cancer treatment doxorubicin
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-020-68999-9
Publisher version: https://doi.org/10.1038/s41598-020-68999-9
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Biomaterials – proteins, Breast cancer, Cancer microenvironment, Cancer models, Experimental models of disease
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10106184
Downloads since deposit
15Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item