Development of a 3D angiogenesis model to study tumour – endothelial cell interactions and the effects of anti-angiogenic drugs

Abstract The tumour microenvironment and tumour angiogenesis play a critical role in the development and therapy of many cancers, but in vitro models reflecting these circumstances are rare. In this study, we describe the development of a novel tri-culture model, using non-small cell lung cancer (NS...

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Autores principales:	Arno Amann, Marit Zwierzina, Stefan Koeck, Gabriele Gamerith, Elisabeth Pechriggl, Julia M. Huber, Edith Lorenz, Jens M. Kelm, Wolfgang Hilbe, Heinz Zwierzina, Johann Kern
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1ee938a72b3246ccbd4db879b442a84b
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spelling	oai:doaj.org-article:1ee938a72b3246ccbd4db879b442a84b2021-12-02T15:04:59ZDevelopment of a 3D angiogenesis model to study tumour – endothelial cell interactions and the effects of anti-angiogenic drugs10.1038/s41598-017-03010-62045-2322https://doaj.org/article/1ee938a72b3246ccbd4db879b442a84b2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03010-6https://doaj.org/toc/2045-2322Abstract The tumour microenvironment and tumour angiogenesis play a critical role in the development and therapy of many cancers, but in vitro models reflecting these circumstances are rare. In this study, we describe the development of a novel tri-culture model, using non-small cell lung cancer (NSCLC) cell lines (A549 and Colo699) in combination with a fibroblast cell line (SV 80) and two different endothelial cell lines in a hanging drop technology. Endothelial cells aggregated either in small colonies in Colo699 containing microtissues or in tube like structures mainly in the stromal compartment of microtissues containing A549. An up-regulation of hypoxia and vimentin, ASMA and a downregulation of E-cadherin were observed in co- and tri-cultures compared to monocultures. Furthermore, a morphological alteration of A549 tumour cells resembling “signet ring cells” was observed in tri-cultures. The secretion of proangiogenic growth factors like vascular endothelial growth factor (VEGF) was measured in supernatants. Inhibition of these proangiogenic factors by using antiangiogenic drugs (bevacizumab and nindetanib) led to a significant decrease in migration of endothelial cells into microtissues. We demonstrate that our method is a promising tool for the generation of multicellular tumour microtissues and reflects in vivo conditions closer than 2D cell culture.Arno AmannMarit ZwierzinaStefan KoeckGabriele GamerithElisabeth PechrigglJulia M. HuberEdith LorenzJens M. KelmWolfgang HilbeHeinz ZwierzinaJohann KernNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Arno Amann Marit Zwierzina Stefan Koeck Gabriele Gamerith Elisabeth Pechriggl Julia M. Huber Edith Lorenz Jens M. Kelm Wolfgang Hilbe Heinz Zwierzina Johann Kern Development of a 3D angiogenesis model to study tumour – endothelial cell interactions and the effects of anti-angiogenic drugs
description	Abstract The tumour microenvironment and tumour angiogenesis play a critical role in the development and therapy of many cancers, but in vitro models reflecting these circumstances are rare. In this study, we describe the development of a novel tri-culture model, using non-small cell lung cancer (NSCLC) cell lines (A549 and Colo699) in combination with a fibroblast cell line (SV 80) and two different endothelial cell lines in a hanging drop technology. Endothelial cells aggregated either in small colonies in Colo699 containing microtissues or in tube like structures mainly in the stromal compartment of microtissues containing A549. An up-regulation of hypoxia and vimentin, ASMA and a downregulation of E-cadherin were observed in co- and tri-cultures compared to monocultures. Furthermore, a morphological alteration of A549 tumour cells resembling “signet ring cells” was observed in tri-cultures. The secretion of proangiogenic growth factors like vascular endothelial growth factor (VEGF) was measured in supernatants. Inhibition of these proangiogenic factors by using antiangiogenic drugs (bevacizumab and nindetanib) led to a significant decrease in migration of endothelial cells into microtissues. We demonstrate that our method is a promising tool for the generation of multicellular tumour microtissues and reflects in vivo conditions closer than 2D cell culture.
format	article
author	Arno Amann Marit Zwierzina Stefan Koeck Gabriele Gamerith Elisabeth Pechriggl Julia M. Huber Edith Lorenz Jens M. Kelm Wolfgang Hilbe Heinz Zwierzina Johann Kern
author_facet	Arno Amann Marit Zwierzina Stefan Koeck Gabriele Gamerith Elisabeth Pechriggl Julia M. Huber Edith Lorenz Jens M. Kelm Wolfgang Hilbe Heinz Zwierzina Johann Kern
author_sort	Arno Amann
title	Development of a 3D angiogenesis model to study tumour – endothelial cell interactions and the effects of anti-angiogenic drugs
title_short	Development of a 3D angiogenesis model to study tumour – endothelial cell interactions and the effects of anti-angiogenic drugs
title_full	Development of a 3D angiogenesis model to study tumour – endothelial cell interactions and the effects of anti-angiogenic drugs
title_fullStr	Development of a 3D angiogenesis model to study tumour – endothelial cell interactions and the effects of anti-angiogenic drugs
title_full_unstemmed	Development of a 3D angiogenesis model to study tumour – endothelial cell interactions and the effects of anti-angiogenic drugs
title_sort	development of a 3d angiogenesis model to study tumour – endothelial cell interactions and the effects of anti-angiogenic drugs
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1ee938a72b3246ccbd4db879b442a84b
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Development of a 3D angiogenesis model to study tumour – endothelial cell interactions and the effects of anti-angiogenic drugs

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