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Structure function relationships in the lymphatic system and implications for cancer biology

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Abstract

The lymphatic system, composed of lymphatic vessels, lymph, lymph nodes, and lymphocytes, is a distinctive vasculature (discontinuous basement membrane, open endothelial junctions, anchoring filaments, valves, and intrinsic contractility), different yet similar to the blood vasculature; an integral component of the plasma-tissue fluid-lymph circulation (the “blood-lymph loop”); and the center of the immunoregulatory network. Lymphatics are involved in diverse developmental, growth, repair, and pathologic processes both analogous to and distinct from those affecting the blood vasculature. Interference with the blood-lymph loop produces swelling [an imbalance between lymph formation (regulated by Starling’s law of transcapillary fluid exchange) and lymph absorption], scarring, nutritional and immunodysregulatory disorders, as well as disturbances in lymph(hem)angiogenesis (lymphedema-angiodysplasia syndromes). The lymphatic system is also the stage on which key events during cancer development and progression are played out, and historically, also forms the basis for current evaluation, prognostication, and/or both operative and non-operative treatment of most cancers. Recent advances in molecular lymphology (e.g., discovery of lymphatic growth factors, endothelial receptors, transcription factors, genes, and highly specific immunohistochemical markers) and growing interest in lymphangiogenesis, combined with fresh insights and refined tools in clinical lymphology, including non-invasive lymphatic imaging, are opening up a window for translation to the clinical arena. Therefore, in cancer biology, attention to the multifaceted structure-function relationships within this vast, relatively unexplored system is long overdue.

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Authors and Affiliations

  1. Department of Surgery, University of Arizona, Tucson, AZ, USA

    Marlys H. Witte

  2. Department of Medicine (Oncology), University of Utah, Salt Lake City, UT, USA

    Kimberly Jones

  3. Department of Pediatrics, University of Göttingen, Germany

    Jörg Wilting

  4. Department of Pathology, Lund University Hospital, Lund, Sweden

    Michael Dictor

  5. Department of Experimental Pathology, Lund University Hospital, Lund, Sweden

    Manuel Selg

  6. Smooth Muscle Research Centre, Dundalk Institute of Technology, Ireland

    Noel McHale

  7. Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Jeffrey E. Gershenwald

  8. Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, UK

    David G. Jackson

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  1. Marlys H. Witte
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  2. Kimberly Jones
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  3. Jörg Wilting
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  5. Manuel Selg
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  8. David G. Jackson
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Correspondence to Marlys H. Witte.

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Presented as Session I of the First International Symposium on Cancer Metastasis and the Lymphovascular System. April 28–30, 2005, San Francisco, CA; Chaired by Marlys H. Witte

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Witte, M.H., Jones, K., Wilting, J. et al. Structure function relationships in the lymphatic system and implications for cancer biology. Cancer Metastasis Rev 25, 159–184 (2006). https://doi.org/10.1007/s10555-006-8496-2

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