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Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells

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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.

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Acknowledgements

This study was supported in part by grants NSC-96-2311-B-006-005-MY3 and NSC-95-2314-B-002-119-MY3 from the National Science Council, DOH-TD-B-111-004 from the Department of Health, CMFHR9405 and CMFHR9542 from the Chi-Mei Medical Center, by funds from a Taiwan Government program promoting academic excellence and the development of world-class research centers, and the Landmark Project of National Cheng Kung University, Taiwan.

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  1. S H Hsieh, N W Ying, T M Hong and Y L Chen: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Oral Medicine, National Cheng Kung University, College of Medicine, Tainan, Taiwan

    S H Hsieh, N W Ying, T Y Wong, Y T Jin & Y L Chen

  2. Institute of Basic Medical Sciences, National Cheng Kung University, College of Medicine, Tainan, Taiwan

    M H Wu & Y L Chen

  3. Oral and Maxillofacial Section, Chi-Mei Medical Center, Tainan, Taiwan

    W F Chiang

  4. Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan

    C L Hsu

  5. The NTU Center for Genomic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

    T M Hong

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  1. S H Hsieh
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  2. N W Ying
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Correspondence to T M Hong or Y L Chen.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Hsieh, S., Ying, N., Wu, M. et al. Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells. Oncogene 27, 3746–3753 (2008). https://doi.org/10.1038/sj.onc.1211029

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