Journal Article

Dose-Dependent Response of FGF-2 for Lymphangiogenesis

Fannon, Michael, Folkman, Judah, Farnebo, Filip, Chang, Lynn K., Mulligan, Richard C., Garcia-Cardeña, Guillermo, Chen, Emy J., Butterfield, Catherine, Moses, Marsha A., Kaipainen, Arja

2004

Overview

Spatio-temporal studies on the growth of capillary blood vessels and capillary lymphatic vessels in tissue remodeling have suggested that lymphangiogenesis is angiogenesis-dependent. We revisited this concept by using fibroblast growth factor 2 (FGF-2) (80 ng) to stimulate the growth of both vessel types in the mouse cornea. When we lowered the dose of FGF-2 in the cornea 6.4-fold (12.5 ng), the primary response was lymphangiogenic. Further investigation revealed that vascular endothelial growth factor-C and -D are required for this apparent lymphangiogenic property of FGF-2, and when the small amount of accompanying angiogenesis was completely suppressed, lymphangiogenesis remained unaffected. Our findings demonstrate that there is a dose-dependent response of FGF-2 for lymphangiogenesis, and lymphangiogenesis can occur in the absence of a preexisting or developing vascular bed, i.e., in the absence of angiogenesis, in the mouse cornea.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Angiogenesis / Animals / Antibodies / Biological Sciences / Blood / Blood vessels / Capillaries / Cell Division - drug effects / Cell Movement - drug effects / Cellular biology / Cornea / Cornea - blood supply / Cornea - physiology / Corneal Neovascularization / Dose-Response Relationship, Drug / Endothelial cells / Endothelial Cells - cytology / Endothelial Cells - drug effects / Endothelium / Fibroblast Growth Factor 2 - pharmacology / Lymphangiogenesis - drug effects / Lymphatic vessels / Male / Mice / Mice, Inbred Strains / Neovascularization, Physiologic - drug effects / RNA / Vascular Endothelial Growth Factor C - pharmacology / Vascular Endothelial Growth Factor D - pharmacology