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The history of the angiogenic switch concept

Leukemia volume 21, pages 44–52 (2007)Cite this article

Abstract

Spontaneously arising tumor cells are not usually angiogenic at first. The phenotypic switch to angiogenesis is usually accomplished by a substet that induces new capillaries that then converge toward the tumor. The switch clearly involves more than simple upregulation of angiogenic activity and is thought to be the result of a net balance of positive and negative regulators. Tumor growth is although to require disruption of this balance and hence this switch must turned on for cancer progression. Progenitor endothelial cells, the crosstalk between angiogenic factors and their receptors and the interaction between vasculogenesis and lymphangiogenesis are all factors that may contribute to the switch. Its promotion is also the outcome of genetic instability resulting in the emergence of tumor cell lines. This review describes the history of the angiogenic switch illustrated in the literature and with particular reference to the three transgenic mouse models, namely RIP1-TAG2, keratin-14 (K14) (human papilloma virus) HPV16 and papilloma virus, used for stage-specific assessment of the effects of antiangiogenic and antitumorigenic agents.

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Acknowledgements

Our studies were supported by Associazione Italiana per la Ricerca sul Cancro (AIRC, National and Regional Funds), Milan, Ministry for Education, the Universities and Research (FIRB 2001 and PRIN 2005), Rome, and Fondazione Italiana per la Lotta al Neuroblastoma, Genoa, Italy.

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  1. Department of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy

    D Ribatti & B Nico

  2. Department of Medical and Morphological Researches, Anatomy Section, University of Udine Medical School, Udine, Italy

    E Crivellato

  3. Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy

    A M Roccaro & A Vacca

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Correspondence to D Ribatti.

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Ribatti, D., Nico, B., Crivellato, E. et al. The history of the angiogenic switch concept. Leukemia 21, 44–52 (2007). https://doi.org/10.1038/sj.leu.2404402

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