The cancer angiogenesis co-culture assay: In vitro quantification of the angiogenic potential of tumoroids.

The treatment response to anti-angiogenic agents varies among cancer patients and predictive biomarkers are needed to identify patients with resistant cancer or guide the choice of anti-angiogenic treatment. We present "the Cancer Angiogenesis Co-Culture (CACC) assay", an in vitro Function...

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Autores principales:	Sarah Line Bring Truelsen, Nabi Mousavi, Haoche Wei, Lucy Harvey, Rikke Stausholm, Erik Spillum, Grith Hagel, Klaus Qvortrup, Ole Thastrup, Henrik Harling, Harry Mellor, Jacob Thastrup
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5310916ac9324f84825d18d85b90f7db
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spelling	oai:doaj.org-article:5310916ac9324f84825d18d85b90f7db2021-12-02T20:05:11ZThe cancer angiogenesis co-culture assay: In vitro quantification of the angiogenic potential of tumoroids.1932-620310.1371/journal.pone.0253258https://doaj.org/article/5310916ac9324f84825d18d85b90f7db2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253258https://doaj.org/toc/1932-6203The treatment response to anti-angiogenic agents varies among cancer patients and predictive biomarkers are needed to identify patients with resistant cancer or guide the choice of anti-angiogenic treatment. We present "the Cancer Angiogenesis Co-Culture (CACC) assay", an in vitro Functional Precision Medicine assay which enables the study of tumouroid induced angiogenesis. This assay can quantify the ability of a patient-derived tumouroid to induce vascularization by measuring the induction of tube formation in a co-culture of vascular cells and tumoroids established from the primary colorectal tumour or a metastasis. Furthermore, the assay can quantify the sensitivity of patient-derived tumoroids to anti-angiogenic therapies. We observed that tube formation increased in a dose-dependent manner upon treatment with the pro-angiogenic factor vascular endothelial growth factor A (VEGF-A). When investigating the angiogenic potential of tumoroids from 12 patients we found that 9 tumoroid cultures induced a significant increase in tube formation compared to controls without tumoroids. In these 9 angiogenic tumoroid cultures the tube formation could be abolished by treatment with one or more of the investigated anti-angiogenic agents. The 3 non-angiogenic tumoroid cultures secreted VEGF-A but we observed no correlation between the amount of tube formation and tumoroid-secreted VEGF-A. Our data suggests that the CACC assay recapitulates the complexity of tumour angiogenesis, and when clinically verified, could prove a valuable tool to quantify sensitivity towards different anti-angiogenic agents.Sarah Line Bring TruelsenNabi MousaviHaoche WeiLucy HarveyRikke StausholmErik SpillumGrith HagelKlaus QvortrupOle ThastrupHenrik HarlingHarry MellorJacob ThastrupPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0253258 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah Line Bring Truelsen Nabi Mousavi Haoche Wei Lucy Harvey Rikke Stausholm Erik Spillum Grith Hagel Klaus Qvortrup Ole Thastrup Henrik Harling Harry Mellor Jacob Thastrup The cancer angiogenesis co-culture assay: In vitro quantification of the angiogenic potential of tumoroids.
description	The treatment response to anti-angiogenic agents varies among cancer patients and predictive biomarkers are needed to identify patients with resistant cancer or guide the choice of anti-angiogenic treatment. We present "the Cancer Angiogenesis Co-Culture (CACC) assay", an in vitro Functional Precision Medicine assay which enables the study of tumouroid induced angiogenesis. This assay can quantify the ability of a patient-derived tumouroid to induce vascularization by measuring the induction of tube formation in a co-culture of vascular cells and tumoroids established from the primary colorectal tumour or a metastasis. Furthermore, the assay can quantify the sensitivity of patient-derived tumoroids to anti-angiogenic therapies. We observed that tube formation increased in a dose-dependent manner upon treatment with the pro-angiogenic factor vascular endothelial growth factor A (VEGF-A). When investigating the angiogenic potential of tumoroids from 12 patients we found that 9 tumoroid cultures induced a significant increase in tube formation compared to controls without tumoroids. In these 9 angiogenic tumoroid cultures the tube formation could be abolished by treatment with one or more of the investigated anti-angiogenic agents. The 3 non-angiogenic tumoroid cultures secreted VEGF-A but we observed no correlation between the amount of tube formation and tumoroid-secreted VEGF-A. Our data suggests that the CACC assay recapitulates the complexity of tumour angiogenesis, and when clinically verified, could prove a valuable tool to quantify sensitivity towards different anti-angiogenic agents.
format	article
author	Sarah Line Bring Truelsen Nabi Mousavi Haoche Wei Lucy Harvey Rikke Stausholm Erik Spillum Grith Hagel Klaus Qvortrup Ole Thastrup Henrik Harling Harry Mellor Jacob Thastrup
author_facet	Sarah Line Bring Truelsen Nabi Mousavi Haoche Wei Lucy Harvey Rikke Stausholm Erik Spillum Grith Hagel Klaus Qvortrup Ole Thastrup Henrik Harling Harry Mellor Jacob Thastrup
author_sort	Sarah Line Bring Truelsen
title	The cancer angiogenesis co-culture assay: In vitro quantification of the angiogenic potential of tumoroids.
title_short	The cancer angiogenesis co-culture assay: In vitro quantification of the angiogenic potential of tumoroids.
title_full	The cancer angiogenesis co-culture assay: In vitro quantification of the angiogenic potential of tumoroids.
title_fullStr	The cancer angiogenesis co-culture assay: In vitro quantification of the angiogenic potential of tumoroids.
title_full_unstemmed	The cancer angiogenesis co-culture assay: In vitro quantification of the angiogenic potential of tumoroids.
title_sort	cancer angiogenesis co-culture assay: in vitro quantification of the angiogenic potential of tumoroids.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/5310916ac9324f84825d18d85b90f7db
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The cancer angiogenesis co-culture assay: In vitro quantification of the angiogenic potential of tumoroids.

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