title: Serum galectin-2, -4, and -8 are greatly increased in colon and breast cancer patients and promote cancer cell adhesion to blood vascular endothelium.
abstract: OBJECTIVE
  Adhesion of disseminating tumor cells to the blood vascular endothelium is a pivotal step in metastasis. Previous investigations have shown that galectin-3 concentrations are increased in the bloodstream of patients with cancer and that galectin-3 promotes adhesion of disseminating tumor cells to vascular endothelium in vitro and experimental metastasis in vivo. This study determined the levels of galectin-1, -2, -3, -4, -8, and -9 in the sera of healthy people and patients with colon and breast cancer and assessed the influence of these galectins on cancer-endothelium adhesion.
  
  
  METHODS
  Serum galectins and auto-anti-MUC1 antibodies were assessed using ELISA and mucin protein (MUC1) glycan microarrays, and cancer-endothelium adhesion was determined using monolayers of human microvascular lung endothelial cells.
  
  
  RESULTS
  The levels of serum galectin-2, -3, -4, and -8 were significantly increased up to 31-fold in patients with cancer and, in particular, those with metastases. As previously shown for galectin-3, the presence of these galectins enhances cancer-endothelium adhesion by interaction with the Thomsen-Friedenreich (TF; Galβ1,3GalNAcα-) disaccharide on cancer-associated MUC1. This causes MUC1 cell surface polarization, thus exposing underlying adhesion molecules that promote cancer-endothelium adhesion. Elevated circulating galectin-2 levels were associated with increased mortality in patients with colorectal cancer, but this association was suppressed when anti-MUC1 antibodies with specificity for the TF epitope of MUC1 were also present in the circulation.
  
  
  CONCLUSIONS
  Increased circulation of several members of the galectin family is common in patients with cancer and these may, like circulating galectin-3, also be involved in metastasis promotion.
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Hannah
authors.initials: H
authors.lastname: Barrow
authors.forename: Xiuli
authors.initials: X
authors.lastname: Guo
authors.forename: Hans H
authors.initials: HH
authors.lastname: Wandall
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Pedersen
authors.forename: Bo
authors.initials: B
authors.lastname: Fu
authors.forename: Qicheng
authors.initials: Q
authors.lastname: Zhao
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Rhodes
authors.forename: Lu-Gang
authors.initials: LG
authors.lastname: Yu
mesh_terms: D001323:Autoantibodies / Q000032:analysis; D001943:Breast Neoplasms / Q000097:blood* / Q000098:blood supply / Q000401:mortality / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000097:blood* / Q000098:blood supply / Q000401:mortality / Q000473:pathology; D004727:Endothelium / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D037501:Galectin 2 / Q000097:blood*; D037541:Galectin 4 / Q000097:blood*; D006801:Humans; D008297:Male; D018396:Mucin-1 / Q000276:immunology / Q000378:metabolism; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*
chemical_list: D001323:Autoantibodies; D037501:Galectin 2; D037541:Galectin 4; C060192:MUC1 protein, human; D018396:Mucin-1