Abstract
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. 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. 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. 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.
Highlights
Adhesion of disseminating tumor cells to the blood vascular endothelium is a crucial step in cancer metastasis and is regulated by various cell surface adhesion molecules/ ligands on cancer cells as well as on vascular endothelial cells [1].Authors' Affiliations: 1Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; 2Department of Pharmacology, School of Pharmacy, Shandong University, Shandong, China; 3Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; and 4School of Community Based Medicine, University of Manchester, Manchester, United KingdomNote: Supplementary data for this article are available at Clinical Cancer Research Online.Ó2011 American Association for Cancer Research.Galectins form a family of 15 mammalian galactosidebinding proteins expressed by many types of human cells
Elevated circulating galectin-2 levels were associated with increased mortality in patients with colorectal cancer, but this association was suppressed when anti-mucin protein 1 (MUC1) antibodies with specificity for the TF epitope of MUC1 were present in the circulation
Increased circulation of several members of the galectin family is common in patients with cancer and these may, like circulating galectin-3, be involved in metastasis promotion
Summary
Galectins form a family of 15 mammalian galactosidebinding proteins expressed by many types of human cells. They are synthesized in the cell cytoplasm from where they can be transported into the cell nucleus, possibly via both active transport and passive diffusion [2], or secreted through a nonclassical pathway [3]. Cytoplasmic galectins are involved in the regulation of cellular apoptosis [4, 5]. The presence of galectin-1 and -3 in the cell nucleus promotes mRNA splicing [6]. The cell surface–associated galectins act as cell adhesion molecules and promote cell–cell and cell–matrix interactions during cancer development and progression [7, 8]
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