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

PURPOSE:

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.

EXPERIMENTAL DESIGN:

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: Hannah Barrow, Xiuli Guo, Hans H Wandall, Johannes W Pedersen, Bo Fu, Qicheng Zhao, Chen Chen, Jonathan M Rhodes, Lu-Gang Yu
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 17 Issue 22 Pg. 7035-46 (Nov 15 2011) ISSN: 1557-3265 [Electronic] United States
• PMID: 21933892 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Galectin 2
• Galectin 4
• MUC1 protein, human
• Mucin-1

Topics

• Autoantibodies (analysis)
• Breast Neoplasms (blood, blood supply, mortality, pathology)
• Cell Adhesion
• Cell Line, Tumor
• Colonic Neoplasms (blood, blood supply, mortality, pathology)
• Endothelium (pathology)
• Endothelium, Vascular (pathology)
• Female
• Galectin 2 (blood)
• Galectin 4 (blood)
• Humans
• Male
• Mucin-1 (immunology, metabolism)
• Neoplasm Metastasis
• Neoplastic Cells, Circulating (pathology)