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Clin Cancer Res. 2013 Apr 1;19(7):1693-704. doi: 10.1158/1078-0432.CCR-12-2940. Epub 2013 Feb 11.

Increased circulation of galectin-3 in cancer induces secretion of metastasis-promoting cytokines from blood vascular endothelium.

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1
Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.

Abstract

PURPOSE:

Cytokines such as interleukin (IL)-6 and granulocyte colony-stimulating factor (G-CSF) are important metastasis promoters. This study has investigated the functional significance of the increased circulation of galectin-3, a common feature in patients with cancer and in particular those with metastasis, on cytokine secretion from the blood vascular endothelium in cancer.

EXPERIMENTAL DESIGN:

The effects of galectin-3 on secretion of cytokines from human microvascular lung endothelial cells were assessed in vitro by cytokine array and in vivo in mice. The consequences of galectin-3-induced cytokine secretion on endothelial cell behaviors were determined, and the relationship between the levels of circulating galectin-3 and cytokines in patients with colorectal cancer with and without metastasis was investigated.

RESULTS:

Galectin-3 at pathologic concentrations found in patients with cancer induces secretion of IL-6, G-CSF, sICAM-1, and granulocyte macrophage colony-stimulating factor from blood vascular endothelial cells in vitro and in mice. These cytokines autocrinely/paracrinely interact with the vascular endothelium to increase the expressions of endothelial cell surface adhesion molecules integrinα(v)β(1), E-selectin, ICAM-1, and VCAM-1, resulting in increased cancer cell-endothelial adhesion and increased endothelial cell migration and tubule formation. In patients with metastatic colon cancer, higher serum galectin-3 levels correlated significantly with increased serum G-CSF, IL-6, and sICAM1 concentrations.

CONCLUSION:

The increased circulation of galectin-3 in patients with cancer induces secretion of several metastasis-promoting cytokines from the blood vascular endothelium that enhances endothelial cell activities in metastasis. Targeting the actions of circulating galectin-3 in patients with cancer therefore represents a promising therapeutic strategy to reduce metastasis and improve survival.

PMID:
23401226
PMCID:
PMC3618858
DOI:
10.1158/1078-0432.CCR-12-2940
[Indexed for MEDLINE]
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