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The Angiogenic Switch in Tumorigenesis

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Tumor Angiogenesis

Abstract

Rapidly growing cancer tissue necessitates an increased blood supply. This is provided mainly by angiogenesis (blood vessel formation from pre-existing vessels) and vasculogenesis (de novo formation of vessels). Vascular co-option and vasculogenic mimicry may also play a role. The transition from a pre-vascular to a vascularized tumor phenotype is called the angiogenic switch. This switch is controlled by a balance between pro-and anti-angiogenic factors, which are secreted by the tumor cells themselves or by cells of the tumor microenvironment (in particular stromal cells and immune cells). The most prominent pro-angiogenic factors are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Conversely, proteolytic fragments of the extracellular matrix (ECM) can act as potent angiogenesis inhibitors (e.g., endostatin). Other anti-angiogenic factors include cleaved derivatives of plasminogen (angiostatin) or antithrombin III (C-terminal antithrombin-fragment). The expression of pro-and anti-angiogenic factors by cancer cells is controlled directly by oncogenes, tumor suppressor genes and transcription factors, but also indirectly by environmental factors (such as oxygen or glucose supply). An important aspect of the angiogenic switch is the susceptibility of endothelial cells to pro-angiogenic stimuli. Genetic and epigenetic changes can modulate the response of the endothelial cells to VEGF and FGF and thus influence the angiogenic balance. Transgenic mouse models have been instrumental in elucidating the angiogenic switch and its effect on tumor progression. In patients, the angiogenic switch has been shown to occur in a number of cancer types, most prominently in breast and cervical cancer.

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Authors and Affiliations

  1. Institute of Biochemistry and Genetics Department of Clinical-Biological Sciences, University of Basel Centre of Biomedicine, Mattenstraße 28, 4058, Basel, Switzerland

    Andreas Wicki

  2. Department of Clinical-Biological Sciences, Institute of Biochemistry and Genetics, Switzerland

    Dr. Gerhard Christofori (Professor)

  3. Center for Biomedicine, University of Basel, Mattenstraße 28, 4058, Basel, Switzerland

    Dr. Gerhard Christofori (Professor)

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  1. Andreas Wicki
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  1. Klinik für Tumorbiologie, Breisacher Str. 117, 79106, Freiburg i. Br., Germany

    Dieter Marmé PhD (Professor) (Professor)

  2. DKFZ, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Norbert Fusenig MD (Professor, former Head of Division of Carcinogenesis and Differentiation) (Professor, former Head of Division of Carcinogenesis and Differentiation)

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Wicki, A., Christofori, G. (2008). The Angiogenic Switch in Tumorigenesis. In: Marmé, D., Fusenig, N. (eds) Tumor Angiogenesis. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-33177-3_4

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  • DOI: https://doi.org/10.1007/978-3-540-33177-3_4

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