title: Evidence for the interaction of fibroblast growth factor-2 with the lymphatic endothelial cell marker LYVE-1.
abstract: LYVE-1 (lymphatic vessel endothelial hyaluronan receptor-1) is a homolog of the hyaluronan receptor CD44, and one of the most widely used markers of lymphatic endothelial cells in normal and tumor tissues. However, the physiologic role of LYVE-1 in the lymphatic system still remains unclear. It is well established that fibroblast growth factor 2 (FGF2) induces lymphangiogenesis. Based on the known interaction between FGF2 and CD44 and based on the structural similarity of CD44 and LYVE-1, we investigated whether FGF2 might interact with LYVE-1. We found that FGF2 is able to bind LYVE-1 using AlphaScreen, or after surface-immobilization or in solution. FGF2 binds to LYVE-1 with a higher affinity than any other known LYVE-1–binding molecules, such as hyaluronan or PDGF-BB. Glycosylation of LYVE-1 is important for FGF2 binding. Furthermore, FGF2 interacts with LYVE-1 when overexpressed in CHO cells. Soluble LYVE-1 and knockdown of LYVE-1 in lymphatic endothelial cells impaired FGF2 signaling and functions. In addition, FGF2 but not VEGF-C-induced in vivo lymphangiogenesis, was also inhibited. Conversely, FGF2 also modulates LYVE-1 expression in cells and ex vivo. Thus, our data demonstrate a functional relationship to the interaction between FGF2 and LYVE-1.
authors.affiliation: Inserm U1029, Talence, France.
authors.forename: Natalia
authors.initials: N
authors.lastname: Platonova
authors.forename: Geraldine
authors.initials: G
authors.lastname: Miquel
authors.forename: Birgit
authors.initials: B
authors.lastname: Regenfuss
authors.forename: Said
authors.initials: S
authors.lastname: Taouji
authors.forename: Claus
authors.initials: C
authors.lastname: Cursiefen
authors.forename: Eric
authors.initials: E
authors.lastname: Chevet
authors.forename: Andreas
authors.initials: A
authors.lastname: Bikfalvi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D042583:Lymphangiogenesis / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D060066:Protein Interaction Maps; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C119248:LYVE1 protein, human; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D033921:Vesicular Transport Proteins; D016222:Fibroblast Growth Factor 2