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 - 2014 Oct 1

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

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cancer Research

Cite this

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.
@article{641a489aaa0b4f7ca55db5ef1e5ee0d5,
title = "Galectin-1 induces vascular permeability through the neuropilin-1/vascular endothelial growth factor receptor-1 complex",
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.",
author = "Wu, {Ming Heng} and Ying, {Nien Wen} and Tse-Ming Hong and Chiang, {Wei Fan} and Lin, {Yueh Te} and Yuh-Ling Chen",
year = "2014",
month = "10",
day = "1",
doi = "10.1007/s10456-014-9431-8",
language = "English",
volume = "17",
pages = "839--849",
journal = "Angiogenesis",
issn = "0969-6970",
publisher = "Springer Netherlands",
number = "4",

}

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

TY - JOUR

T1 - Galectin-1 induces vascular permeability through the neuropilin-1/vascular endothelial growth factor receptor-1 complex

AU - Wu, Ming Heng

AU - Ying, Nien Wen

AU - Hong, Tse-Ming

AU - Chiang, Wei Fan

AU - Lin, Yueh Te

AU - Chen, Yuh-Ling

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84907591496&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907591496&partnerID=8YFLogxK

U2 - 10.1007/s10456-014-9431-8

DO - 10.1007/s10456-014-9431-8

M3 - Article

VL - 17

SP - 839

EP - 849

JO - Angiogenesis

JF - Angiogenesis

SN - 0969-6970

IS - 4

ER -