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Cell and Tissue Research

, Volume 314, Issue 1, pp 167–177 | Cite as

Lymphangiogenesis and tumor metastasis

  • Michael S. PepperEmail author
  • Jean-Christophe Tille
  • Riccardo Nisato
  • Mihaela Skobe
Review

Abstract

The lymphatic system transports interstitial fluid and macromolecules from tissues back to the blood circulation, and plays an important role in the immune response by directing the traffic of lymphocytes and antigen-presenting cells. The lymphatic system also constitutes one of the most important pathways of tumor dissemination. In many human cancers, increased expression of vascular endothelial growth factor-C (VEGF-C) is correlated with regional lymph node metastases. Experimental studies using transgenic mice overexpressing VEGF-C or xenotransplantation of VEGF-C-expressing tumor cells into immunodeficient mice have demonstrated a role for VEGF-C in tumor lymphangiogenesis and the subsequent formation of lymph node metastases. However, there is at present little evidence for lymphangiogenesis in human tumors and the relative importance of preexisting vs. newly formed lymphatics for metastasis in humans remains to be determined. Nonetheless, the striking correlation between the levels of VEGF-C in primary human tumors and lymph node metastases predicts its importance in cancer spread. Aside from promoting lymphangiogenesis, VEGF-C may also activate lymphatics to promote tumor cell chemotaxis, lymphatic intravasation and hence tumor cell dissemination.

Keywords

Cancer Metastasis Lymphangiogenesis VEGF-C VEGFR-3 

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Michael S. Pepper
    • 1
    Email author
  • Jean-Christophe Tille
    • 1
  • Riccardo Nisato
    • 1
  • Mihaela Skobe
    • 2
  1. 1.Department of MorphologyUniversity Medical CenterGeneva 4Switzerland
  2. 2.Derald H. Ruttenberg Cancer CenterMount Sinai School of MedicineNew YorkUSA

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