title: Glucose Promotes a Pro-Oxidant and Pro-Inflammatory Stromal Microenvironment Which Favors Motile Properties in Breast Tumor Cells.
abstract: Chronic inflammation and metabolic reprogramming have been proposed as hallmarks of cancer development. Currently, many of the functional clues between these two phenomena are studied under the integrative view of functional stroma-epithelia interaction. It has been proposed that stromal cells, due to their abundance and avidity for glucose, are able to modify the metabolic behavior of an entire solid tumor. In the present study, using a mammary stromal cell line derived from healthy tissue subjected to long-term culture in low (5 mM) or high (25 mM) glucose, we found that the hyperglycemic condition favors the establishment of a pro-inflammatory and pro-oxidant environment characterized by the induction of the COX-2/PGE2 axis. In this condition, epithelial migration was stimulated. Moreover, we also found that stromal-derived PGE2, acting as a stimulator of IL-1 epithelial expression was one of the factors that promote the acquisition of motile properties by epithelial cells and the maintenance of a COX-2/PGE2-dependent inflammatory condition. Overall, our work provides experimental evidence that glucose stimulates a tumor inflammatory environment that, as a result of a functional cross-talk between stroma and epithelia, may be responsible for tumor progression. J. Cell. Biochem. 118: 994-1002, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Laboratorio de Biología Celular y Molecular, INTA, Universidad de Chile, Santiago 7830490, Chile.
authors.forename: Violeta
authors.initials: V
authors.lastname: Kallens
authors.affiliation: Laboratorio de Biología Celular y Molecular, INTA, Universidad de Chile, Santiago 7830490, Chile.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Tobar
authors.affiliation: Laboratorio de Biología Celular y Molecular, INTA, Universidad de Chile, Santiago 7830490, Chile.
authors.forename: Jessica
authors.initials: J
authors.lastname: Molina
authors.affiliation: Laboratorio de Biología Celular y Molecular, INTA, Universidad de Chile, Santiago 7830490, Chile.
authors.forename: Arantzazú
authors.initials: A
authors.lastname: Bidegain
authors.affiliation: Laboratorio de Fisiología Periodontal, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile.
authors.forename: Patricio C
authors.initials: PC
authors.lastname: Smith
authors.affiliation: Laboratorio de Biología Celular y Molecular, INTA, Universidad de Chile, Santiago 7830490, Chile.
authors.forename: Omar
authors.initials: O
authors.lastname: Porras
authors.affiliation: Laboratorio de Biología Celular y Molecular, INTA, Universidad de Chile, Santiago 7830490, Chile.
authors.forename: Jorge
authors.initials: J
authors.lastname: Martínez
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D061986:MCF-7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D007375:Interleukin-1; D017382:Reactive Oxygen Species; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D005947:Glucose; D015232:Dinoprostone
keywords: BREAST CANCER; COX-2; GLUCOSE; IL-1; INFLAMMATION; STROMA