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Peritumor lymphatics induced by vascular endothelial growth factor-C exhibit abnormal function
Naohide Isaka1, Timothy P Padera, Jeroen Hagendoorn
1E. L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Cancer Research
|July 3, 2004
Summary
Vascular endothelial growth factor (VEGF)-C promotes lymphatic hyperplasia. New lymphatic vessels in tumors show retrograde flow, suggesting valve dysfunction.
Area of Science:
- Oncology
- Vascular Biology
- Cancer Research
Background:
- Vascular endothelial growth factor (VEGF)-C is known to induce lymphatic hyperplasia.
- The function of these hyperplastic peritumor lymphatics requires examination.
Purpose of the Study:
- To investigate the function of hyperplastic peritumor lymphatics in VEGF-C-overexpressing tumors.
- To assess the lymphatic drainage patterns and cellular proliferation within these vessels.
Main Methods:
- Utilized microlymphangiography in a murine dorsal skinfold chamber model.
- Quantified functional, draining lymphatics in B16F10 melanoma tumors.
- Analyzed lymphatic endothelial cell proliferation and drainage patterns.
Main Results:
- VEGF-C-overexpressing tumors exhibited a significantly greater number of functional, draining lymphatics compared to controls (9.5 vs. 6.3).
- Forty percent of functional lymphatics associated with VEGF-C-overexpressing tumors contained proliferating lymphatic endothelial cells.
- A surprising retrograde draining pattern was observed in newly formed lymphatic vessels, indicating potential intraluminal valve dysfunction.
Conclusions:
- VEGF-C induces hyperplasia and proliferation of peritumor lymphatics.
- Newly formed lymphatic vessels in VEGF-C-overexpressing tumors may exhibit impaired function due to valve abnormalities.
- Further research is needed to understand the implications of lymphatic valve dysfunction in cancer progression.