P5-07-04: Is a-L-Fucose Overexpressed on Cells of Aggressive Human Breast Cancers?

Abstract

Abstract Enzymatic removal of a-L-fucose (fucose) was shown over 20 years ago to abolish metastases in vivo in a rat model of mammary adenocarcinoma [J Cell Biochem 1988; 37: 49–59]. Since that time, evidence has accumulated to indicate that fucose is a functional effector in human breast cancer; essential for construction of the invasive and metastatic phenotypes. In light of these findings, the role of fucose in aggressive breast cancers is worthy of further investigation. Our group has modified the method of Wright et al. in order to selectively remove cell surface fucose from viable human breast cancer cells in vitro. In our experience, a 30 min incubation of breast cancer cells with α-L-fucosidase (3.2.1.51) leads to a loss of transformative abilities including decreased cancer cell adhesion to select extracellular matrix components, decreased invasion into complex extracellular matrices, decreased binding by relevant antibodies and lectins, and decreased adhesion of cells (rolling) to model endothelium under shear stress flow conditions. From this work we postulated that decisive differences in phenotypic and functional properties between treated and control human breast cancer cells should be obtainable with currently available models of aggressive disease. To that end, we and others have subsequently shown that human breast cancer cells express cell surface CD44 which carries fucosylated ligands and that its’ defucosylation altered its’ malignant phenotype.. Based on these precedents, it is reasonable to hypothesize that CD44-enriched breast cancer stem cell populations require fucose in order to exert their aggressive behavior. Assays to assess the role of fucose in these stem cells are apparent and include a battery of tests involving stem cell invasion into extracellular matrices, cell binding of antibodies or fucolectins, stem cell aggregation into spheroids, colony formation in soft agar, assessment of stem cell rolling/adhesion to endothelial cells or purified E-selectin under both static or physiological flow conditions and the ability to initiate tumors upon inoculation into animal models. We believe that new insights into aggressive breast cancer cell behaviors can be gained through the depletion of cell surface fucose from breast cancer cells. Knowledge gained from these studies should yield new insights when using current models of human breast cancer in vitro and in vivo. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-07-04.