Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 278, Issue 6, Pages 4127-4134Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M209590200
Keywords
-
Categories
Funding
- NCI NIH HHS [CA86290-01, 1R43CA72284, 1R01CA89827-01] Funding Source: Medline
- NIAID NIH HHS [1R01AI35796] Funding Source: Medline
Ask authors/readers for more resources
The importance of Thomsen-Friedenreich antigen (T antigen)-galectin-3 interactions in adhesion of human breast carcinoma cells to the endothelium under conditions of flow was studied. Highly metastatic cells (MDA-MB-435) expressing high levels of both galectin-3 and T antigen demonstrated significantly increased adhesion to monolayers of endothelial cells compared with their non-metastatic counterpart (MDA-MB-468) in vitro. Within minutes of adhesion, the highly metastatic cells acquire the ability of enhanced homotypic adhesion, leading to the formation of multicellular aggregates at sites of attachment to endothelial cells in vitro. Treatment of cells with lactulosyl-L-leucine, a synthetic T antigen antagonist that targets galectin-3 by mimicking T antigen, caused a 60-80% inhibition of both homo- and heterotypic adhesion of MDA-MB-435 cells. Confocal microscopy and fluorescence-activated cell sorter analysis revealed redistribution of endothelial galectin-3 to the site of heterotypic intercellular contacts, whereas galectin-3 in MDA-MB-435 cells accumulated at sites of homotypic interaction. MDA-MB-435 cells also exhibited increased adhesion and intravascular retention within the microvessels of transplanted lung allografts in nude mice. T antigen and galectin-3-mediated interactions of metastatic cancer cells with endothelium under conditions of flow are characterized by a unique adhesion mechanism that qualitatively distinguishes their homo-and heterotypic adhesive behavior from other cell types such as leukocytes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available