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

Research output: Contribution to journalJournal articlepeer-review


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

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 tumouroinduced angiogenesis. This assay can quantify the ability of a patient-derived tumouroto 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 antiangiogenic 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 tumorocultures induced a significant increase in tube formation compared to controls without tumoroids. In these 9 angiogenic tumorocultures the tube formation could be abolished by treatment with one or more of the investigated anti-angiogenic agents. The 3 non-angiogenic tumorocultures 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.

Original languageEnglish
Article numbere0253258
JournalPLoS ONE
Issue number7 July
Number of pages22
Publication statusPublished - Jul 2021

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Copyright © 2021 Truelsen et al.

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