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The anti-angiogenic tyrosine kinase inhibitor Pazopanib kills cancer cells and disrupts endothelial networks in biomimetic 3D renal tumouroids

Stamati, K; Redondo, PA; Nyga, A; Neves, JB; Tran, M; Emberton, M; Cheema, U; (2020) The anti-angiogenic tyrosine kinase inhibitor Pazopanib kills cancer cells and disrupts endothelial networks in biomimetic 3D renal tumouroids. Journal of Tissue Engineering , 11 10.1177/2041731420920597. Green open access

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Abstract

Pazopanib is a tyrosine kinase inhibitor used to treat renal cell carcinoma. Few in vitro studies investigate its effects towards cancer cells or endothelial cells in the presence of cancer. We tested the effect of Pazopanib on renal cell carcinoma cells (CAKI-2,786-O) in two-dimensional and three-dimensional tumouroids made of dense extracellular matrix, treated in normoxia and hypoxia. Finally, we engineered complex tumouroids with a stromal compartment containing fibroblasts and endothelial cells. Simple CAKI-2 tumouroids were more resistant to Pazopanib than 786-O tumouroids. Under hypoxia, while the more ‘resistant’ CAKI-2 tumouroids showed no decrease in viability, 786-O tumouroids required higher Pazopanib concentrations to induce cell death. In complex tumouroids, Pazopanib exposure led to a reduction in the overall cell viability (p < 0.0001), disruption of endothelial networks and direct killing of renal cell carcinoma cells. We report a biomimetic multicellular tumouroid for drug testing, suitable for agents whose primary target is not confined to cancer cells.

Type: Article
Title: The anti-angiogenic tyrosine kinase inhibitor Pazopanib kills cancer cells and disrupts endothelial networks in biomimetic 3D renal tumouroids
Open access status: An open access version is available from UCL Discovery
DOI: 10.1177/2041731420920597
Publisher version: https://doi.org/10.1177/2041731420920597
Language: English
Additional information: Creative Commons CC BY: This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
Keywords: 2D versus 3D culture, in vitro endothelial networks, Pazopanib, renal cell carcinoma, tumouroid
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 Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
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 Ortho and MSK Science
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/10094449
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