Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth.
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.
Karpanen
T
T
Molecular/Cancer Biology Laboratory, Haartman Institute and Ludwig Institute for Cancer Research, University of Helsinki, Finland.
Egeblad
M
M
Karkkainen
M J
MJ
Kubo
H
H
Ylä-Herttuala
S
S
Jäättelä
M
M
Alitalo
K
K
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D008208:Lymphatic System / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology*; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D014162:Transfection; D014183:Transplantation, Heterologous; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3
D016228:Endothelial Growth Factors; D007136:Immunoglobulins; D017978:Receptors, Growth Factor; D011993:Recombinant Fusion Proteins; D042582:Vascular Endothelial Growth Factor C; D020794:Receptor Protein-Tyrosine Kinases; D040321:Vascular Endothelial Growth Factor Receptor-3