PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis

Cancer Cell. 2004 Oct;6(4):333-45. doi: 10.1016/j.ccr.2004.08.034.


Cancer metastases are commonly found in the lymphatic system. Like tumor blood angiogenesis, stimulation of tumor lymphangiogenesis may require the interplay of several tumor-derived growth factors. Here we report that members of the PDGF family act as lymphangiogenic factors. In vitro, PDGF-BB stimulated MAP kinase activity and cell motility of isolated lymphatic endothelial cells. In vivo, PDGF-BB potently induced growth of lymphatic vessels. Expression of PDGF-BB in murine fibrosarcoma cells induced tumor lymphangiogenesis, leading to enhanced metastasis in lymph nodes. These data demonstrate that PDGF-BB is an important growth factor contributing to lymphatic metastasis. Thus, blockage of PDGF-induced lymphangiogenesis may provide a novel approach for prevention and treatment of lymphatic metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Becaplermin
  • Cell Division / drug effects
  • Cell Line
  • Chemotaxis / drug effects
  • Female
  • Humans
  • Lymphangiogenesis / drug effects*
  • Lymphatic Metastasis*
  • Lymphatic System / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / pathology*
  • Organ Size / drug effects
  • Platelet-Derived Growth Factor / pharmacology*
  • Proto-Oncogene Proteins c-sis
  • Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Receptors, Vascular Endothelial Growth Factor / genetics
  • Signal Transduction / drug effects
  • Vascular Endothelial Growth Factor A / pharmacology


  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • Vascular Endothelial Growth Factor A
  • platelet-derived growth factor A
  • platelet-derived growth factor AB
  • Becaplermin
  • Receptors, Platelet-Derived Growth Factor
  • Receptors, Vascular Endothelial Growth Factor