1. ¹Institute of Oral Medicine, National Cheng Kung University, College of Medicine, Tainan, Taiwan
2. ²Institute of Basic Medical Sciences, National Cheng Kung University, College of Medicine, Tainan, Taiwan
3. ³Oral and Maxillofacial Section, Chi-Mei Medical Center, Tainan, Taiwan
4. ⁴Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan
5. ⁵The NTU Center for Genomic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

Correspondence: Dr YL Chen, Institute of Oral Medicine, National Cheng Kung University, College of Medicine, 1 University Road, Tainan 70101, Taiwan. E-mail: yuhling@mail.ncku.edu.tw; Dr TM Hong, The NTU Center for Genomic Medicine, College of Medicine, National Taiwan University, 1, Sec1, Jen Ai Road, Taipei, Taiwan. E-mail: htm@gate.sinica.edu.tw

⁶These authors contributed equally to this work.

Received 13 September 2007; Revised 26 November 2007; Accepted 10 December 2007; Published online 28 January 2008.

Abstract

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 VEGF₁₆₅. 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 VEGF₁₆₅. 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.