title: Metabolism under hypoxia in Tm1 murine melanoma cells is affected by the presence of galectin-3, a metabolomics approach.
abstract: Metabolomics has proven an useful tool for systems biology. Here we have used a metabolomics approach to identify conditions in which de novo expression of an established tumor marker, galectin-3, would confer a potential selective advantage for melanoma growth and survival. A murine melanoma cell line (Tm1) that lacks galectin-3 was modified to express it or not (Tm1.G2 and Tm1.N3, respectively). These variant cell line were then exposed to conditions of controlled oxygen tensions and glucose levels. Metabolic profiling of intracellular metabolites of cells exposed to these conditions was obtained in steady state using high resolution (1)H Magnetic Resonance Spectroscopy ((1)H-MRS) and multivariate statistical analysis. The Nuclear Magnetic Resonance (NMR) spectra contained a large number of absorption lines from which we were able to distinguish 20 metabolites, 3 fatty acids and some absorption lines and clusters were not identified. Principal Components Analysis (PCA) allowed for the discrimination of 2 experimental conditions in which expression of the tumor marker galectin-3 may play a significant role, namely exposure of cells to hypoxia under high glucose. Interestingly, under all other experimental conditions tested, the cellular system was quite robust. Our results suggest that the Metabolomics approach can be used to access information about changes in many metabolic pathways induced in tumorigenic cells and to allow the evaluation of their behavior in controlled environmental conditions or selective pressures.
authors.affiliation: Laboratório de Oncologia Experimental and Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo and Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 251, CEP 01246-000 São Paulo, Brazil.
authors.forename: Pedro Starzynski
authors.initials: PS
authors.lastname: Bacchi
authors.affiliation: Laboratório de Ressonância Magnética, Instituto de Física da Universidade de São Paulo, R. do Matão trav. R, 187, CEP 05508-090 São Paulo, Brazil.
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Bloise
authors.affiliation: Laboratório de Oncologia Experimental and Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo and Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 251, CEP 01246-000 São Paulo, Brazil.
authors.forename: Silvina Odete
authors.initials: SO
authors.lastname: Bustos
authors.affiliation: Laboratório de Oncologia Experimental and Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo and Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 251, CEP 01246-000 São Paulo, Brazil.
authors.forename: Lara
authors.initials: L
authors.lastname: Zimmermann
authors.affiliation: Laboratório de Oncologia Experimental and Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo and Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 251, CEP 01246-000 São Paulo, Brazil.
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.affiliation: Laboratório de Ressonância Magnética, Instituto de Física da Universidade de São Paulo, R. do Matão trav. R, 187, CEP 05508-090 São Paulo, Brazil.
authors.forename: Said Rahnamaye
authors.initials: SR
authors.lastname: Rabbani
keywords: 1H-MRS; Galectin-3; Melanoma; Metabolomics; NMR; PCA; Tm1.G2; Tm1.N3; Warburg effect