Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells.
Galectin-1 (Gal-1), a homodimeric prototype of the galectins with a single carbohydrate-recognition domain, was recently identified as being overexpressed in tumor-associated capillary endothelial cells. The role of Gal-1 in endothelial cellular functions and the mechanism of action of Gal-1 remain unknown. Neuropilin-1 (NRP1) is a neuronal receptor that mediates repulsive growth cone guidance, and NRP1 functions in endothelial cells as a coreceptor (with vascular endothelial growth factor receptors (VEGFRs)) for VEGF(165). In this study, we found that Gal-1 was overexpressed in the tumor-associated endothelial cells of oral squamous cell carcinomas (P<0.001). Gal-1 increased the proliferation and adhesion of endothelial cells, and enhanced cell migration in combination with VEGF(165). Surprisingly, Gal-1 selectively bound NRP1 via the carbohydrate-recognition domain, but did not bind VEGFR-1, VEGFR-2 or VEGFR-3. The Gal-1-NRP1 interaction mediated the migration and adhesion of endothelial cells. The binding of Gal-1 to NRP1 enhanced VEGFR-2 phosphorylation and stimulated the activation of the mitogen activated protein (MAP) kinases SAPK1/JNK (stress activated protein kinase-1/c-Jun NH2-terminal kinase). These findings show, for the first time, that Gal-1 can directly bind to NRP1 on endothelial cells, and can promote the NRP1/VEGFR-2-mediated signaling pathway as well as NRP1-mediated biological activities.
Hsieh
S H
SH
Institute of Oral Medicine, National Cheng Kung University, College of Medicine, Tainan, Taiwan.
Ying
N W
NW
Wu
M H
MH
Chiang
W F
WF
Hsu
C L
CL
Wong
T Y
TY
Jin
Y T
YT
Hong
T M
TM
Chen
Y L
YL
D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D042783:Endothelial Cells / Q000502:physiology*; D037483:Galectin 1 / Q000032:analysis / Q000502:physiology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009062:Mouth Neoplasms / Q000473:pathology; D039942:Neuropilin-1 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000502:physiology*
D037483:Galectin 1; D039942:Neuropilin-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D048031:JNK Mitogen-Activated Protein Kinases