title: Modulation of the uptake of critical nutrients by breast cancer cells by lactate: Impact on cell survival, proliferation and migration.
abstract: This work aimed to characterize the uptake of folate and glucose by breast cancer cells and to study the effect of lactate upon the transport of these nutrients and upon cell viability, proliferation and migration capacity. Data obtained showed that: a) MCF7 cells uptake (3)H-folic acid ((3)H-FA) at physiological but not at acidic pH; b) T47D cells accumulate (3)H-FA and (14)C-5-methyltetrahydrofolate ((14)C-5-MTHF) more efficiently at acidic than at physiological pH; c) (3)H-deoxyglucose ((3)H-DG) uptake by T47D cells is sodium-independent, inhibited by cytochalasin B (CYT B) and stimulated by insulin. Regarding the effect of lactate, in T47D cells, acute (26 min) and chronic (24 h) exposure to lactic acid (LA) stimulated (3)H-FA uptake. Acute exposure to LA also stimulated (3)H-DG uptake and chronic exposure to LA significantly stimulated T47D cell migratory capacity. In conclusion, the transport of folates is strikingly different in two phenotypically similar breast cancer cell lines: MCF7 and T47D cells. Additionally, lactate seems to act as a signaling molecule which increases the uptake of nutrients and promotes the migration capacity of T47D cells.
authors.affiliation: Department of Biochemistry, Faculty of Medicine of University of Porto, 4200-319 Porto, Portugal; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Guedes
authors.affiliation: Department of Biochemistry, Faculty of Medicine of University of Porto, 4200-319 Porto, Portugal; Institut Pasteur, INSERM U786, Unité de Pathogénie Microbienne Moléculaire, 75015 Paris, France.
authors.forename: João R
authors.initials: JR
authors.lastname: Araújo
authors.affiliation: Department of Biochemistry, Faculty of Medicine of University of Porto, 4200-319 Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Correia-Branco
authors.affiliation: Department of Biochemistry, Faculty of Medicine of University of Porto, 4200-319 Porto, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Gregório
authors.affiliation: Department of Biochemistry, Faculty of Medicine of University of Porto, 4200-319 Porto, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Martel
authors.affiliation: Department of Biochemistry, Faculty of Medicine of University of Porto, 4200-319 Porto, Portugal; Center for Biotechnology and Fine Chemistry, School of Biotechnology, Portuguese Catholic University, 4200-072 Porto, Portugal; CINTESIS, Center for Research in Health Technologies and Information Systems, University of Porto, 4200-319 Porto, Portugal. Electronic address: keating@med.up.pt.
authors.forename: Elisa
authors.initials: E
authors.lastname: Keating
mesh_terms: D001692:Biological Transport / Q000502:physiology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D002470:Cell Survival; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*
chemical_list: D019344:Lactic Acid; D005492:Folic Acid; D005947:Glucose
keywords: Breast cancer; Folate uptake; Glucose uptake; Lactate; Warburg effect