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. 2023 Feb 10;23:24. doi: 10.1186/s12935-022-02837-y

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© The Author(s) 2023

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — Angiogenesis HIF-1, which leads to the secretion of pro-angiogenic factors, now the most significant of which being VEGF. Hypoxia also causes basement membrane disintegration and pericyte datachment by increasing protease expression. Angiogenic factor gradients attract specialized endothelial cells. Endothelial cells are transformed into strongly proliferative stalk cells that form the new vessel’s main body. DLL4 production is stimulated by VEGF, that interacts to Notch-1 receptors and suppresses Vascular Endothelial Growth Factor receptor (VEGFR). Pericyte attachment is stimulated by PDGF, which lowers proliferation and sensitivity to VEGF. Tumor growth is aided by the availability of blood. EGF epidermal growth factor, FGF fibroblast growth factors, TGF-β transforming growth factor beta, HIF-1 hypoxia activates hypoxia-inducible factor 1; VEGF: vascular endothelial growth factor, DLL4 delta-like 4, PDGF platelet-derived growth factor, IGF1 insulin-like growth factor 1