title: 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 beta-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 microenvironment of tumor cells may negatively affect the outcome for some breast cancer patients.
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. karbassi@uams.edu
authors.forename: Behjatolah
authors.initials: B
authors.lastname: Monzavi-Karbassi
authors.forename: R Jean
authors.initials: RJ
authors.lastname: Hine
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Stanley
authors.forename: Vishnu Prakash
authors.initials: VP
authors.lastname: Ramani
authors.forename: Jaime
authors.initials: J
authors.lastname: Carcel-Trullols
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Whitehead
authors.forename: Thomas
authors.initials: T
authors.lastname: Kelly
authors.forename: Eric R
authors.initials: ER
authors.lastname: Siegel
authors.forename: Cecile
authors.initials: C
authors.lastname: Artaud
authors.forename: Saeid
authors.initials: S
authors.lastname: Shaaf
authors.forename: Rinku
authors.initials: R
authors.lastname: Saha
authors.forename: Fariba
authors.initials: F
authors.lastname: Jousheghany
authors.forename: Ronda
authors.initials: R
authors.lastname: Henry-Tillman
authors.forename: Thomas
authors.initials: T
authors.lastname: Kieber-Emmons
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002244:Carbon / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008858:Microscopy, Phase-Contrast; D009361:Neoplasm Invasiveness; D010641:Phenotype; D037121:Plant Lectins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
chemical_list: D000199:Actins; D037121:Plant Lectins; D005632:Fructose; D002244:Carbon