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

Author:

Truelsen Sarah Line BringORCID,Mousavi Nabi,Wei Haoche,Harvey Lucy,Stausholm Rikke,Spillum Erik,Hagel Grith,Qvortrup Klaus,Thastrup Ole,Harling Henrik,Mellor Harry,Thastrup JacobORCID

Abstract

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.

Funder

Innovation fond Denmark

Agnes og Poul Friis Fond

C.C. Klestrup & Hustrus Henriette Klestrups Mindelegat

Carl & Ellen Hertz legat til dansk læge- og naturvidenskab

The Drost Fundation

Familien Hede Nielsens Fond

Publisher

Public Library of Science (PLoS)

Subject

Multidisciplinary

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