Vv. Glinsky et al., The role of Thomsen-Friedenreich antigen in adhesion of human breast and prostate cancer cells to the endothelium, CANCER RES, 61(12), 2001, pp. 4851-4857
Interactions of metastatic cancer cells with vasculatory endothelium are cr
itical during early stages of cancer metastasis, Understanding the molecula
r underpinnings of these interactions is essential for the development of n
ew 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 an
tigen-bearing glycoproteins are also capable of mobilizing galectin-3 to th
e surface of endothelial cells, thus priming them for harboring metastatic
cancer cells. The T antigen-mediated, tumor-endothelial cell interactions c
ould be efficiently disrupted using synthetic compounds either mimicking or
masking this carbohydrate structure. High efficiency of T antigen-mimickin
g and T antigen-masking inhibitors of tumor cell adhesion warrants their fu
rther development into antiadhesive cancer therapeutics.