title: Increased circulation of galectin-3 in cancer induces secretion of metastasis-promoting cytokines from blood vascular endothelium.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors: Chen
authors: C
authors: Chen
authors: Carrie A
authors: CA
authors: Duckworth
authors: Qicheng
authors: Q
authors: Zhao
authors: David Mark
authors: DM
authors: Pritchard
authors: Jonathan M
authors: JM
authors: Rhodes
authors: Lu-Gang
authors: LG
authors: Yu
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D037502:Galectin 3 / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D037502:Galectin 3
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