Targeting neovascularization and respiration of tumor grafts grown on chick embryo chorioallantoic membranes.
Since growing tumors stimulate angiogenesis, via vascular endothelial growth factor (VEGF), angiogenesis inhibitors (AIs, blockers of the VEGF signaling pathway) have been introduced to cancer therapy. However, AIs often yielded only modest and short-lived gains in cancer patients and more invasive...
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oai:doaj.org-article:4d0d39519819418880f3c2187cac7b0b2021-11-25T06:19:12ZTargeting neovascularization and respiration of tumor grafts grown on chick embryo chorioallantoic membranes.1932-620310.1371/journal.pone.0251765https://doaj.org/article/4d0d39519819418880f3c2187cac7b0b2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251765https://doaj.org/toc/1932-6203Since growing tumors stimulate angiogenesis, via vascular endothelial growth factor (VEGF), angiogenesis inhibitors (AIs, blockers of the VEGF signaling pathway) have been introduced to cancer therapy. However, AIs often yielded only modest and short-lived gains in cancer patients and more invasive tumor phenotypes in animal models. Combining anti-VEGF strategies with lactate uptake blockers may boost both efficacy and safety of AIs. We assessed this hypothesis by using the ex ovo chorioallantoic membrane (CAM) assay. We show that AI-based monotherapy (Avastin®, AVA) increases tumor hypoxia in human CAM cancer cell xenografts and cell spread in human as well as canine CAM cancer cell xenografts. In contrast, combining AVA treatment with lactate importer MCT1 inhibitors (α-cyano-4-hydroxycinnamic acid (CHC) or AZD3965 (AZD)) reduced both tumor growth and cell dissemination of human and canine explants. Moreover, combining AVA+AZD diminished blood perfusion and tumor hypoxia in human explants. Thus, the ex ovo CAM assay as an easy, fast and cheap experimental setup is useful for pre-clinical cancer research. Moreover, as an animal-free experimental setup the CAM assay can reduce the high number of laboratory animals used in pre-clinical cancer research.Hyrije AdemiDheeraj A ShindeMax GassmannDaniela GerstHassan ChaachouayJohannes VogelThomas A GorrPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251765 (2021) |
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Medicine R Science Q Hyrije Ademi Dheeraj A Shinde Max Gassmann Daniela Gerst Hassan Chaachouay Johannes Vogel Thomas A Gorr Targeting neovascularization and respiration of tumor grafts grown on chick embryo chorioallantoic membranes. |
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Since growing tumors stimulate angiogenesis, via vascular endothelial growth factor (VEGF), angiogenesis inhibitors (AIs, blockers of the VEGF signaling pathway) have been introduced to cancer therapy. However, AIs often yielded only modest and short-lived gains in cancer patients and more invasive tumor phenotypes in animal models. Combining anti-VEGF strategies with lactate uptake blockers may boost both efficacy and safety of AIs. We assessed this hypothesis by using the ex ovo chorioallantoic membrane (CAM) assay. We show that AI-based monotherapy (Avastin®, AVA) increases tumor hypoxia in human CAM cancer cell xenografts and cell spread in human as well as canine CAM cancer cell xenografts. In contrast, combining AVA treatment with lactate importer MCT1 inhibitors (α-cyano-4-hydroxycinnamic acid (CHC) or AZD3965 (AZD)) reduced both tumor growth and cell dissemination of human and canine explants. Moreover, combining AVA+AZD diminished blood perfusion and tumor hypoxia in human explants. Thus, the ex ovo CAM assay as an easy, fast and cheap experimental setup is useful for pre-clinical cancer research. Moreover, as an animal-free experimental setup the CAM assay can reduce the high number of laboratory animals used in pre-clinical cancer research. |
format |
article |
author |
Hyrije Ademi Dheeraj A Shinde Max Gassmann Daniela Gerst Hassan Chaachouay Johannes Vogel Thomas A Gorr |
author_facet |
Hyrije Ademi Dheeraj A Shinde Max Gassmann Daniela Gerst Hassan Chaachouay Johannes Vogel Thomas A Gorr |
author_sort |
Hyrije Ademi |
title |
Targeting neovascularization and respiration of tumor grafts grown on chick embryo chorioallantoic membranes. |
title_short |
Targeting neovascularization and respiration of tumor grafts grown on chick embryo chorioallantoic membranes. |
title_full |
Targeting neovascularization and respiration of tumor grafts grown on chick embryo chorioallantoic membranes. |
title_fullStr |
Targeting neovascularization and respiration of tumor grafts grown on chick embryo chorioallantoic membranes. |
title_full_unstemmed |
Targeting neovascularization and respiration of tumor grafts grown on chick embryo chorioallantoic membranes. |
title_sort |
targeting neovascularization and respiration of tumor grafts grown on chick embryo chorioallantoic membranes. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doaj.org/article/4d0d39519819418880f3c2187cac7b0b |
work_keys_str_mv |
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