Dose-dependent response of FGF-2 for lymphangiogenesis

Abstract

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.

Induction of lymphangiogenesis through vascular endothelial growth factor-C/vascular endothelial growth factor receptor 3 axis and its correlation with lymph node metastasis in nasopharyngeal carcinoma

“…Chang, et al reported that FGF-2 stimulates the proliferation, migration and tube formation of isolated lymphatic endothelial cells, indicating a direct role in lymphatic vessel growth [38] . In addition, COX-2 demonstrates a positive regulatory role in lymphangiogenesis [39] .…”

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

“…FGF2 pellets implanted in the mouse cornea trigger both angiogenesis and lymphangiogenesis, lymphatic vessels being more sensitive than blood vessels to FGF2 [110]. However, the lymphangiogenic activity of FGF2 is mediated by endogenous VEGF-C and VEGF-D upregulation, leading to VEGFR-3 activation [111]. Interestingly, no endothelial fenestration was observed in FGF2, VEGF-A, or VEGF-C-induced lymphatic vessels [112].…”

Advances in the research on lymphangiogenesis in carcinoma tissues (Review)

“…In a mouse corneal model, FGF-2 facilitated lymphangiogenesis, and the effect was indirectly elicited by the activation of the VEGF-C/VEGF-D/ VEGFR-3 signaling pathways (28).…”