Fructose as a carbon source induces an aggressive phenotype in MDA-MB-468 breast tumor cells

Abstract

Aberrant glycosylation is a universal feature of cancer cells, and certain glycan structures are well-known markers for tumor progression. Availability and composition of sugars in the microenvironment may affect cell glycosylation. Recent studies of human breast tumor cell lines indicate their ability to take up and utilize fructose. Here we tested the hypothesis that adding fructose to culture as a carbon source induces phenotypic changes in cultured human breast tumor cells that are associated with metastatic disease. MDA-MB-468 cells were adapted to culture media in which fructose was substituted for glucose. Changes in cell surface glycan structures, expression of genes related to glycan assembly, cytoskeleton F-actin, migration, adhesion and invasion were determined. Cells cultured in fructose expressed distinct cell-surface glycans. The addition of fructose affected sialylation and fucosylation patterns. Fructose feeding also increased binding of leukoagglutinating Phaseolus vulgaris isolectin, suggesting a possible rise in expression of branching β-1, 6 GlcNAc structures. Rhodamine-phalloidin staining revealed an altered F-actin cytoskeletal system. Fructose accelerated cellular migration and increased invasion. These data suggest that changing the carbon source of the less aggressive MDA-MB-468 cell line induced characteristics associated with more aggressive phenotypes. These data could be of fundamental importance due to the markedly increased consumption of sweeteners containing free fructose in recent years, as they suggest that the presence of fructose in nutritional micro-environment of tumor cells may negatively affect the outcome for some breast cancer patients.

A Sucrose-Enriched Diet Promotes Tumorigenesis in Mammary Gland in Part through the 12-Lipoxygenase Pathway

“…3b). This is consistent with literature that described that fructose is associated with more aggressive/metastatic phenotype of breast cancer cells (24) and its transporters (GLUT2 and GLUT5) are linked to numerous diseases and syndromes including breast cancer (25). Strikingly, while sucrose diet continually increased the breast tumor 12-HETE production (289.3±65.6 ng/mg protein), average tumor 12-HETE concentration was significantly higher in tumors from mice fed with fructose (333.1±58.6 ng/mg protein) and with fructose plus glucose diets (521.3±57.3 ng/mg protein) compared to the 12-HETE levels in control diet fed mice (186.2±25.5 ng/mg protein) (Fig.…”

Enhanced Fructose Utilization Mediated by SLC2A5 Is a Unique Metabolic Feature of Acute Myeloid Leukemia with Therapeutic Potential

“…Fructose has previously been reported to alter the glycan structures on the cell surface of tumor cells and increase their proliferative and invasive properties when compared to glucose in vitro (Monzavi-Karbassi et al, 2010). Our data demonstrated that altered fructose utilization plays a key role in AML progression as evidenced by an exacerbated leukemic phenotype regardless of the concentration of glucose present.…”

Dairy intake in relation to breast and pubertal development in Chilean girls,

“…Biologically, intake of sugar enhances cellular proliferation and migration, induces DNA damage, and increases inflammation (44). Furthermore, an in vitro study on breast tumor cells showed that, although fructose appears to increase cell invasion and migration, glucose seems to increase cell proliferation (45). Excessive sugar consumption is also associated with an increase in the production of insulin that could increase IGF-I (46), which is a growth factor that has mitogenic and antiapoptotic effects on cells (47).…”