title: Modulation of Mammary Stromal Cell Lactate Dynamics by Ambient Glucose and Epithelial Factors.
abstract: Hyperglycemia is a risk factor for a variety of human cancers. Increased access to glucose and that tumor metabolize glucose by a glycolytic process even in the presence of oxygen (Warburg effect), provide a framework to analyze a particular set of metabolic adaptation mechanisms that may explain this phenomenon. In the present work, using a mammary stromal cell line derived from healthy tissue that was subjected to a long-term culture in low (5 mM) or high (25 mM) glucose, we analyzed kinetic parameters of lactate transport using a FRET biosensor. Our results indicate that the glucose pre-culture and soluble epithelial factors constitute a stimulus for lactate stromal production, factors that also modify the kinetic parameters and the monocarboxylate transporters expression in stromal cells. We also observed a vectorial flux of lactate from stroma to epithelial cells in a co-culture setting and found that the uptake of lactate by epithelial cells correlates with the degree of malignancy. Glucose preconditioning of the stromal cell stimulated epithelial motility. Our findings suggest that lactate generated by stromal cells in the high glucose condition stimulate epithelial migration. Overall, our results support the notion that glucose not only provides a substrate for tumor nutrition but also behaves as a signal promoting malignancy. J. Cell. Physiol. 232: 136-144, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Laboratorio de Biología Celular, INTA, Universidad de Chile, Santiago, Chile.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tobar
authors.affiliation: Laboratorio de Biología Celular, INTA, Universidad de Chile, Santiago, Chile.
authors.forename: Omar
authors.initials: O
authors.lastname: Porras
authors.affiliation: Laboratorio de Fisiología Periodontal, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Patricio C
authors.initials: PC
authors.lastname: Smith
authors.affiliation: Centro de Estudios Científicos, Valdivia, Chile.
authors.forename: L Felipe
authors.initials: LF
authors.lastname: Barros
authors.affiliation: Laboratorio de Biología Celular, INTA, Universidad de Chile, Santiago, Chile. jmartine@inta.uchile.cl.
authors.forename: Jorge
authors.initials: J
authors.lastname: Martínez
mesh_terms: D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D042361:Mammary Glands, Human / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: D019344:Lactic Acid; D005947:Glucose