A new study has found that blocking vascular endothelial growth factor receptor 3 (VEGFR-3) prevented lymphangiogenesis in a mouse model but had no effect on blood angiogenesis or the survival or function of existing lymphatic vessels. Specifically targeting VEGFR-3 may inhibit tumor metastasis by preventing lymphatic vessel growth by the tumor, the study concludes.
VEGFR-3 plays an important role in embryonic and tumor lymphatic vessel growth. Neutralization of the growth factors that activate VEGFR-3 was known to inhibit lymphangiogenesis in tumors and to reduce metastasis to lymph nodes. These observations suggested that antagonists of VEGFR-3 activation could inhibit lymphangiogenesis thus preventing or reducing tumor metastasis. It was not known whether new lymphatic growth could be specifically blocked without also affecting blood angiogenesis or existing lymphatic vessels.
Melody A. Swartz, Ph.D., of Northwestern University in Chicago (currently of the Swiss Federal Institute of Technology Lausanne), and colleagues demonstrate in a mouse model of skin regeneration that blocking VEGFR-3 activation with a novel antibody, mF4-31C1, can completely and specifically prevent lymphangiogenesis while leaving blood angiogenesis and existing lymphatic vessels unaffected.
"These findings raise the possibility that human VEGFR-3 may be targeted therapeutically to prevent the undesirable growth of lymphatic vessels, such as tumor-induced lymphatic hyperplasia or lymphangiogenesis," the authors write.
In an editorial, Yoshiyawu Aoki and Giovanna Tosato, M.D., of the National Cancer Institute, discuss the known signaling pathways by which VEFGR-3 is activated and its biologic function in normal and disease processes and note the importance of the new findings.