Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis

Metastasis of breast cancer occurs primarily through the lymphatic system, and the extent of lymph node involvement is a key prognostic factor for the disease. Whereas the significance of angiogenesis for tumor progression has been well documented, the ability of tumor cells to induce the growth of...

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Bibliographic Details
Published in:Nature medicine Vol. 7; no. 2; pp. 192 - 198
Main Authors: Skobe, Mihaela, Hawighorst, Thomas, Jackson, David G., Prevo, Remko, Janes, Lauren, Velasco, Paula, Riccardi, Lucia, Alitalo, Kari, Claffey, Kevin, Detmar, Michael
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.02.2001
Nature Publishing Group
Subjects:
Animals
Biomedical and Life Sciences
Biomedicine
Breast cancer
Breast Neoplasms - pathology
Cancer Research
Endothelial Growth Factors - genetics
Endothelial Growth Factors - physiology
Female
Humans
Infectious Diseases
Lung Neoplasms - pathology
Lung Neoplasms - secondary
Lymph Nodes
Lymphatic Metastasis
Metabolic Diseases
Mice
Mice, Nude
Molecular Medicine
Neoplasm Metastasis
Neovascularization, Pathologic
Neurosciences
Tumor Cells, Cultured
Tumors
Vascular Endothelial Growth Factor C
ISSN:1078-8956, 1546-170X
Online Access:Get full text
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Summary:Metastasis of breast cancer occurs primarily through the lymphatic system, and the extent of lymph node involvement is a key prognostic factor for the disease. Whereas the significance of angiogenesis for tumor progression has been well documented, the ability of tumor cells to induce the growth of lymphatic vessels (lymphangiogenesis) and the presence of intratumoral lymphatic vessels have been controversial. Using a novel marker for lymphatic endothelium, LYVE-1, we demonstrate here the occurrence of intratumoral lymphangiogenesis within human breast cancers after orthotopic transplantation onto nude mice. Vascular endothelial growth factor (VEGF)-C overexpression in breast cancer cells potently increased intratumoral lymphangiogenesis, resulting in significantly enhanced metastasis to regional lymph nodes and to lungs. The degree of tumor lymphangiogenesis was highly correlated with the extent of lymph node and lung metastases. These results establish the occurrence and biological significance of intratumoral lymphangiogenesis in breast cancer and identify VEGF-C as a molecular link between tumor lymphangiogenesis and metastasis.
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ISSN:1078-8956
1546-170X
DOI:10.1038/84643