Lymphangiogenesis in Cancer: Current Perspectives
Although the lymphatic system has been initially described in the sixteenth century, basic research has been limited. Despite its importance for the maintenance of tissue fluid homeostasis and for the afferent immune response, research of the molecular me
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Rüediger Liersch, Christoph Biermann, Rolf M. Mesters, and Wolfgang E. Berdel
Abstract Although the lymphatic system has been initially described in the sixteenth century, basic research has been limited. Despite its importance for the maintenance of tissue fluid homeostasis and for the afferent immune response, research of the molecular mechanisms of lymphatic vessel formation and function has for a long time been hampered. One reason could be because of the difficulties of visibility due to the lack of lymphatic markers. But since the discovery of several molecules specifically expressed in lymphatic endothelial cells, a rediscovery of the lymphatic vasculature has taken place. New scientific insights has facilitated detailed analysis of the nature and organization of the lymphatic system in physiological and pathophysiological conditions, such as in chronic inflammation and metastatic cancer spread. Knowledge about the molecules that control lymphangiogenesis and tumor-associated lymphangiogenesis is now expanding,
R. Liersch (*) Department of Medicine, Hematology/Oncology, University Hospital Münster, Albert-Schweitzer-str. 33, 48129, Münster, Germany e-mail: [email protected]
allowing better opportunities for the development of drugs interfering with the relevant signaling pathways. Advances in our understanding of the mechanisms have translated into a number of novel therapeutic studies.
8.1 Introduction The lymphatic vasculature develops separately, but is functionally related to the blood vascular system. While the blood vascular system is a closed circulatory system, the lymphatic system is open-ended. It collects the interstitial fluid in the periphery and drains the absorbed lymph in the nuchal region into the subclavian veins. This loop controls the balance of various factors and 10% of the body fluid volume. Next to the transport of interstitial fluid, the lymphatic system plays an essential role in the circulation of macromolecules, dietary fats, lymphocytes, and antigenpresenting cells. In the immune-regulatory network, the lymphatic system directs the trafficking of cytokines and immune cells. However, the lymphatic system is also a common pathway for lymphatic metastasis, and therefore plays an essential role for overall survival of cancer patients.
R. Liersch et al. (eds.), Angiogenesis Inhibition, Recent Results in Cancer Research, DOI: 10.1007/978-3-540-78281-0_8, © Springer Verlag Berlin Heidelberg 2010
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8.2 Embryonic Lymphatic Development The lymphatic system develops in parallel with the blood vascular system, but although major progress has been made, it remains controversial as to whether the lymphatic vasculature is developing from embryonic veins, from lymphangioblasts, or from both (Wilting et al. 1999). In 1902, Florence Sabin proposed the most widely accepted theory that the lymphatic vasculature develops from embryonic veins (Sabin 1902; Sabin 1904) and that the peripheral lymphatic system expands from the primary lymph sacs, originates from vascular
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