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: Natalia Platonova, Geraldine Miquel, Birgit Regenfuss, Said Taouji, Claus Cursiefen, Eric Chevet, Andreas Bikfalvi
• Journal: Blood (Blood) Vol. 121 Issue 7 Pg. 1229-37 (Feb 14 2013) ISSN: 1528-0020 [Electronic] United States
• PMID: 23264596 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• CD44 protein, human
• Hyaluronan Receptors
• LYVE1 protein, human
• RNA, Small Interfering
• Recombinant Proteins
• Vesicular Transport Proteins
• Fibroblast Growth Factor 2

Topics

• Animals
• Biomarkers (metabolism)
• CHO Cells
• Cell Line
• Cricetinae
• Cricetulus
• Endothelial Cells (drug effects, metabolism)
• Fibroblast Growth Factor 2 (administration & dosage, genetics, metabolism)
• Human Umbilical Vein Endothelial Cells
• Humans
• Hyaluronan Receptors (metabolism)
• Lymphangiogenesis (drug effects, physiology)
• Mice
• Mice, Inbred BALB C
• Protein Interaction Maps
• RNA, Small Interfering (genetics)
• Recombinant Proteins (administration & dosage, genetics, metabolism)
• Vesicular Transport Proteins (administration & dosage, antagonists & inhibitors, genetics, metabolism)