Significance of Lymphangiogenesis for Metastatic Spread of Breast Cancer
Abstract
The lymphatic system serves as the primary route for the metastasis of breast cancer, and the extent of lymph node involvement is a key prognostic factor for the outcome of 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 questioned. We demonstrate occurrence of intratumoral lymphangiogenesis within human breast cancers alter orthotopic transplantation onto nude mice, using a novel marker for lymphatic endothelium, LYVE-1-I. We show using green fluorescent protein-tagging that breast tumor cells which overexpress vascular endothelial growth factor-C (VEGF-C), display a potent increase in intratumoral lymphangiogenesis, and significantly enhanced metastasis to both regional lymph nodes and lungs. Furthermore we have found that the degree of tumor lymphangiogenesis is highly correlated with the extent of both 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2002
- Accession Number
- ADA412780
Entities
People
- Mihaela Skobe
Organizations
- Icahn School of Medicine at Mount Sinai