Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth

Cancer Res. 2001 Mar 1;61(5):1786-90.

Abstract

Many solid tumors produce vascular endothelial growth factor C (VEGF-C), and its receptor, VEGFR-3, is expressed in tumor blood vessels. To study the role of VEGF-C in tumorigenesis, we implanted MCF-7 human breast carcinoma cells overexpressing recombinant VEGF-C orthotopically into severe combined immunodeficient mice. VEGF-C increased tumor growth, but unlike VEGF, it had little effect on tumor angiogenesis. Instead, VEGF-C strongly promoted the growth of tumor-associated lymphatic vessels, which in the tumor periphery were commonly infiltrated with the tumor cells. These effects of VEGF-C were inhibited by a soluble VEGFR-3 fusion protein. Our data suggest that VEGF-C facilitates tumor metastasis via the lymphatic vessels and that tumor spread can be inhibited by blocking the interaction between VEGF-C and its receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / blood supply*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Division / physiology
  • Endothelial Growth Factors / antagonists & inhibitors
  • Endothelial Growth Factors / biosynthesis
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / physiology*
  • Female
  • Humans
  • Immunoglobulins / biosynthesis
  • Immunoglobulins / blood
  • Immunoglobulins / genetics
  • Lymphatic System / pathology*
  • Mice
  • Mice, SCID
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / physiopathology*
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Receptor Protein-Tyrosine Kinases / blood
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptors, Growth Factor / biosynthesis
  • Receptors, Growth Factor / blood
  • Receptors, Growth Factor / genetics
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / blood
  • Recombinant Fusion Proteins / genetics
  • Transfection
  • Transplantation, Heterologous
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor Receptor-3

Substances

  • Endothelial Growth Factors
  • Immunoglobulins
  • Receptors, Growth Factor
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor C
  • Receptor Protein-Tyrosine Kinases
  • Vascular Endothelial Growth Factor Receptor-3