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Angiogenesis – Vessels Recruitment by Tumor Cells

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Molecular and Cell Biology of Cancer

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Abstract

In this chapter you will learn that tumor blood vessels play important roles in tumor progression and that targeting the tumor vasculature is an alternative cancer therapy. Blood vessels are formed by endothelial cells organized in a monolayer, attached to a basement membrane and covered by pericytes. In general, endothelial cells are adherent to each other through molecular complexes that form the adherens and tight junctions. Such adhesion complexes guarantee the barrier function of the endothelial monolayer, crucial for the regulated transport of molecules and cells between the blood and the tissue and vice-versa. Blood vessels are essential for cell survival as they bring oxygen and nutrients to cells and also participate in the transport of waste products away from tissues. In that sense, as tumors grow, through the rapid proliferation of tumor cells, they require the formation of a new vasculature that irrigates the cells. Without a new vasculature, tumor cells are too far away from a vascular bed, which results in hypoxia and nutrient starvation. These are believed to be the main triggers of new blood vessel formation. The formation of a new blood vessel from a pre-existing one is called angiogenesis and is the main type of blood vessel formation that takes place in tumors. However, other ways to ensure blood deliver to tumor cells have been described. Angiogenesis also occurs in physiological conditions such as during development and wound closure and several cellular and molecular mechanisms that govern it have been elucidated. The most common experimental models used to study physiological angiogenesis are the mouse retina, the transparent zebrafish and human endothelial cells cultured in in vitro systems. The vascular Endothelial Growth Factor (VEGF) is the main signaling molecule that regulates angiogenesis, although several other pro- and anti-angiogenic stimuli exist. In tumors, due to an imbalance of such stimuli, angiogenesis is abnormal, resulting in a disorganized and leaky vascular network. The abnormal nature of the tumor vasculature plays critical roles in cancer progression, in particular its inadequate ability to ensure the barrier function of the vessels has several pathological consequences and is an obstacle to the delivery of therapeutic drugs to tumors. Abnormally permeable blood vessels allow the uncontrolled movement of molecules, extracellular vesicles and cells, in and out of the tumor. This is the starting point for cancer to become a systemic disease. Through leaky blood vessels, tumors send signals to distant tissues, recruit and control immune response and invade the blood through a process called intravasation. Targeting blood vascular formation in tumors or its interaction with tumor and immune cells, or instead, normalize the otherwise abnormal tumor vessels, are alternatives for anti-cancer therapies.

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Authors and Affiliations

  1. Instituto de Medicina Molecular – João Lobo Antunes, Lisbon, Portugal

    Ana Magalhães & Sergio Dias

  2. Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal

    Sergio Dias

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  1. Ana Magalhães
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  2. Sergio Dias
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Correspondence to Ana Magalhães .

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  1. Champalimaud Centre for the Unknown, Champalimaud Foundation, Lisbon, Portugal

    Rita Fior

  2. Faculdade de Ciências da Universidade de Lisboa, Lisbon, Portugal

    Rita Zilhão

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Magalhães, A., Dias, S. (2019). Angiogenesis – Vessels Recruitment by Tumor Cells. In: Fior, R., Zilhão, R. (eds) Molecular and Cell Biology of Cancer. Learning Materials in Biosciences. Springer, Cham. https://doi.org/10.1007/978-3-030-11812-9_8

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