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Galectin-1 induces vascular permeability through the neuropilin-1/vascular endothelial growth factor receptor-1 complex

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Abstract

Galectin-1 (Gal-1) is a β-galactoside-binding lectin that regulates endothelial cell migration, proliferation, and adhesion. However, the effect of Gal-1 on vascular permeability and the underlying mechanisms are unclear. We found that high Gal-1 expression was associated with elevated tumor vascular permeability in specimens of oral squamous cell carcinoma. Using transendothelial passage of FITC-dextran and a Miles assay, we demonstrated that Gal-1 increased vascular permeability extracellularly through its carbohydrate recognition domain. Mechanism dissection revealed that the neuropilin (NRP)-1/vascular endothelial growth factor receptor- (VEGFR)-1 complex was required for Gal-1-regulated vascular permeability. Activation of VEGFR-1 triggered activation of Akt which led to a reduction in vascular endothelial-cadherin at cell–cell junctions and resulted in cytoskeletal rearrangement. Both inhibition of Gal-1 secreted from cancer cells and administration of an anti-Gal-1 antibody in the tumor microenvironment suppressed tumor growth and vascular permeability in xenograft models. In conclusion, our results demonstrate a novel function of Gal-1 of increasing vascular permeability through the NRP-1/VEGFR1 and Akt signaling pathway and indicate that targeting Gal-1 by an anti-Gal-1 antibody is a feasible therapy for vascular hyperpermeability and cancer.

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Acknowledgments

RNAi reagents were obtained from the National RNAi Core Facility, Institute of Molecular Biology/Genomic Research Center, Academia Sinica, which was supported by a grant (NSC97-3112-B-001-016) from the National Research Program for Genomic Medicine Grants of National Science Council (Taipei, Taiwan). Thanks for the human samples from the Tissue Bank and Bioinformatics Core Lab, Research Center of Clinical Medicine, National Cheng Kung University Hospital, (Tainan, Taiwan), and Human Tumor Tissue Bank, Chi-Mei Medical Center (Liouying, Taiwan). We thank Mr. C. Changou from Image Core of Taipei Medical University providing the assistance of the confocal microscopy. This work was supported by grants NSC101-2320-B-006-026-MY3, NSC102-2325-B-006-016, and NSC102-2320-B-038-004 from the National Science Council, Taiwan; grants TMU101-AE1-B42 and TMU101-AE3-Y20 from Taipei Medical University.

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No potential conflicts of interest are declared.

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Authors and Affiliations

  1. Graduate Institute of Translational Medicine, College of Medical Sciences and Technology, Taipei Medical University, Taipei, Taiwan

    Ming-Heng Wu

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

    Ming-Heng Wu, Nien-Wen Ying & Yuh-Ling Chen

  3. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Tse-Ming Hong

  4. Oral and Maxillofacial Section, Chi-Mei Medical Center, Liouying, Taiwan

    Wei-Fan Chiang

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

    Yueh-Te Lin & Yuh-Ling Chen

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  1. Ming-Heng Wu
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Correspondence to Yuh-Ling Chen.

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Wu, MH., Ying, NW., Hong, TM. et al. Galectin-1 induces vascular permeability through the neuropilin-1/vascular endothelial growth factor receptor-1 complex. Angiogenesis 17, 839–849 (2014). https://doi.org/10.1007/s10456-014-9431-8

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  • DOI: https://doi.org/10.1007/s10456-014-9431-8

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