Cancer and Metastasis Reviews

, Volume 25, Issue 2, pp 159–184 | Cite as

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

  • Marlys H. WitteEmail author
  • Kimberly Jones
  • Jörg Wilting
  • Michael Dictor
  • Manuel Selg
  • Noel McHale
  • Jeffrey E. Gershenwald
  • David G. Jackson


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.


Lymphatic system Structure-function Cancer biology Metastasis Lymphatic embryology Stem cells Lymphatic contractility Lymphatic endothelium Sentinel nodes Lymphatic markers Tumor lymphangiogenesis 


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Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Marlys H. Witte
    • 1
    Email author
  • Kimberly Jones
    • 2
  • Jörg Wilting
    • 3
  • Michael Dictor
    • 4
  • Manuel Selg
    • 5
  • Noel McHale
    • 6
  • Jeffrey E. Gershenwald
    • 7
  • David G. Jackson
    • 8
  1. 1.Department of SurgeryUniversity of ArizonaTucsonUSA
  2. 2.Department of Medicine (Oncology)University of UtahSalt Lake CityUSA
  3. 3.Department of PediatricsUniversity of GöttingenGermany
  4. 4.Department of PathologyLund University HospitalLundSweden
  5. 5.Department of Experimental PathologyLund University HospitalLundSweden
  6. 6.Smooth Muscle Research CentreDundalk Institute of TechnologyIreland
  7. 7.Department of Surgical OncologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  8. 8.Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe HospitalUniversity of OxfordUK

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