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

Marlys H. Witte, Kimberly Jones, Jörg Wilting, Michael Dictor, Manuel Selg, Noel McHale, Jeffrey E. Gershenwald, David G. Jackson

Research output: Contribution to journalArticlepeer-review

95 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)159-184
Number of pages26
JournalCancer and Metastasis Reviews
Issue number2
StatePublished - Jun 2006


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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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