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

Karpanen, T., Egeblad, M., Karkkainen, M. J., Kubo, H., Yla-Herttuala, S., Jaattela, M., Alitalo, K. (March 2001) Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Research, 61 (5). pp. 1786-90. ISSN 0008-5472 (Print)0008-5472



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.

Item Type: Paper
Uncontrolled Keywords: Animals Breast Neoplasms/*blood supply/genetics/metabolism/pathology Cell Division/physiology Endothelial Growth Factors/antagonists & inhibitors/biosynthesis/genetics/*physiology Female Humans Immunoglobulins/biosynthesis/blood/genetics Lymphatic System/*pathology Mice Mice, SCID Neoplasm Transplantation Neovascularization, Pathologic/metabolism/*physiopathology Receptor Protein-Tyrosine Kinases/biosynthesis/blood/genetics Receptors, Growth Factor/biosynthesis/blood/genetics Recombinant Fusion Proteins/biosynthesis/blood/genetics Transfection Transplantation, Heterologous Vascular Endothelial Growth Factor C Vascular Endothelial Growth Factor Receptor-3
Subjects: diseases & disorders > cancer > cancer types > breast cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Vascular endothelial growth factor
CSHL Authors:
Communities: CSHL labs > Egeblad lab
Depositing User: Matt Covey
Date: 1 March 2001
Date Deposited: 05 Dec 2014 16:42
Last Modified: 05 Dec 2014 16:42
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