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

Ming Heng Wu, Nien Wen Ying, Tse Ming Hong, Wei Fan Chiang, Yueh Te Lin, Yuh Ling Chen

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)839-849
Number of pages11
JournalAngiogenesis
Volume17
Issue number4
DOIs
Publication statusPublished - Oct 1 2014

Fingerprint

Neuropilin-1
Galectin 1
Vascular Endothelial Growth Factor Receptor-1
Capillary Permeability
Tumors
Neoplasms
Chemical activation
Galactosides
Dissection
Intercellular Junctions
Tumor Microenvironment
Antibodies
Endothelial cells
Lectins
Heterografts
Cell Adhesion
Cell Movement
Blood Vessels
Squamous Cell Carcinoma
Assays

Keywords

  • Galectin-1
  • Neuropilin-1
  • Oral cancer
  • Vascular permeability

ASJC Scopus subject areas

  • Cancer Research
  • Physiology
  • Clinical Biochemistry
  • Medicine(all)

Cite this

Galectin-1 induces vascular permeability through the neuropilin-1/vascular endothelial growth factor receptor-1 complex. / Wu, Ming Heng; Ying, Nien Wen; Hong, Tse Ming; Chiang, Wei Fan; Lin, Yueh Te; Chen, Yuh Ling.

In: Angiogenesis, Vol. 17, No. 4, 01.10.2014, p. 839-849.

Research output: Contribution to journalArticle

Wu, Ming Heng ; Ying, Nien Wen ; Hong, Tse Ming ; Chiang, Wei Fan ; Lin, Yueh Te ; Chen, Yuh Ling. / Galectin-1 induces vascular permeability through the neuropilin-1/vascular endothelial growth factor receptor-1 complex. In: Angiogenesis. 2014 ; Vol. 17, No. 4. pp. 839-849.
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