The role of Thomsen-Friedenreich antigen in adhesion of human breast and prostate cancer cells to the endothelium.
Interactions of metastatic cancer cells with vasculatory endothelium are critical during early stages of cancer metastasis. Understanding the molecular underpinnings of these interactions is essential for the development of new efficacious cancer therapies. Here we demonstrate that cancer-associated carbohydrate T antigen plays a leading role in docking breast and prostate cancer cells onto endothelium by specifically interacting with endothelium-expressed beta-galactoside-binding protein, galectin-3. Importantly, T antigen-bearing glycoproteins are also capable of mobilizing galectin-3 to the surface of endothelial cells, thus priming them for harboring metastatic cancer cells. The T antigen-mediated, tumor-endothelial cell interactions could be efficiently disrupted using synthetic compounds either mimicking or masking this carbohydrate structure. High efficiency of T antigen-mimicking and T antigen-masking inhibitors of tumor cell adhesion warrants their further development into antiadhesive cancer therapeutics.
Glinsky
V V
VV
Department of Biochemistry, University of Missouri, Columbia, Missouri 65211, USA.
Glinsky
G V
GV
Rittenhouse-Olson
K
K
Huflejt
M E
ME
Glinskii
O V
OV
Deutscher
S L
SL
Quinn
T P
TP
D000595:Amino Acid Sequence; D000943:Antigens, Differentiation / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000502:physiology*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000096:biosynthesis / Q000502:physiology*; D001853:Bone Marrow / Q000098:blood supply; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005260:Female; D037502:Galectin 3; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology*
D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D000939:Epitopes; D037502:Galectin 3; D010446:Peptide Fragments; C016467:Thomsen-Friedenreich antigen