The cancer angiogenesis co-culture assay: In vitro quantification of the angiogenic potential of tumoroids
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The cancer angiogenesis co-culture assay : In vitro quantification of the angiogenic potential of tumoroids. / Truelsen, Sarah Line Bring; Mousavi, Nabi; Wei, Haoche; Harvey, Lucy; Stausholm, Rikke; Spillum, Erik; Hagel, Grith; Qvortrup, Klaus; Thastrup, Ole; Harling, Henrik; Mellor, Harry; Thastrup, Jacob.
In: PLoS ONE, Vol. 16, No. 7 July, e0253258, 07.2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The cancer angiogenesis co-culture assay
T2 - In vitro quantification of the angiogenic potential of tumoroids
AU - Truelsen, Sarah Line Bring
AU - Mousavi, Nabi
AU - Wei, Haoche
AU - Harvey, Lucy
AU - Stausholm, Rikke
AU - Spillum, Erik
AU - Hagel, Grith
AU - Qvortrup, Klaus
AU - Thastrup, Ole
AU - Harling, Henrik
AU - Mellor, Harry
AU - Thastrup, Jacob
N1 - Publisher Copyright: Copyright © 2021 Truelsen et al.
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pone.0253258
DO - 10.1371/journal.pone.0253258
M3 - Journal article
C2 - 34234354
AN - SCOPUS:85109482113
VL - 16
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 7 July
M1 - e0253258
ER -
ID: 274569040