MSACL 2019 EU Abstract
Self-Classified Topic Area(s): Lipidomics
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 Lipidomic Profiling of Colorectal Cancer Cell Lines under Hypoxia
Juan Carlos Alarcon-Barrera. (1), Evelyne Steenvoorden (1), Oleg A mayboroda (1), Martin Giera (1)
(1) LUMC, Leiden, Netherlands
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Presenter Bio: My name is Juan Carlos Alarcon Barrera and I was born in Colombia, South America, I have a bachelor degree in Chemistry and a Master degree in Biochemistry from Universidad Nacional in Colombia. During my bachelor and master, I researched on cancer biology, mainly focused on cellular stress and cell signaling. Since two years ago, I joined the CPM department at LUMC as a Ph.D. student. Under the supervision of Dr. Martin Giera, I have worked on metabolomics and lipidomics of mammalian cells using NMR and the Lipidyzer platform. My research project is to study the metabolome, lipidome, and proteome of cancer cells in co-culture with fibroblast and hypoxia. The aim of this study is to determine how metabolism regulates cancer progression, and, in the long term, to select candidates for cancer treatment.
No relevant financial relationship(s) to disclose.
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Abstract INTRODUCTION: Colorectal cancer (CRC) is the third and second most common cancer occurring in men and women respectively. During CRC development, the tumor microenvironment has shown to be a key component to sustain progress and spreading of the tumor. The tumor microenvironment is a complex and dynamic matrix in which different cell types interact with each other to sustain tumor growth. In addition, this dynamic system shows fluctuation in physicochemical conditions. Hypoxia is a well-known state during tumor development responsible for metabolic adaptation, and promotion of tumor invasion. However, the role and mechanisms by which hypoxia induces lipid re-modeling are still not understood. Nevertheless, this regulation is related to tumor and stroma phenotype key players to better understand the tumor-microenvironment.
OBJECTIVES: The primary objective of this study was to describe changes in the lipid profiling of four colorectal cancer cell lines after 24 hours of incubation under hypoxia.
METHODS: Four colorectal cancer cell (CRC) lines, HT29, HCT116, SW480, and LS174T, were seeded and grown to almost 80% confluency, subsequently the cells were incubated in a hypoxia incubator at 1% O2 for 24 hours. After incubation, lipids were extracted and quantitatively measured with a QTRAP 5500 system and SelexION Technology, using the Lipidyzer platform from SCIEX. Data were analyzed using GraphPad and Metaboanalyst, changes were noted comparing normoxia (20% O2) versus hypoxia.
RESULTS: Lipid profiling of the four cancer cell lines at basal state showed clustering according to disease stage. During hypoxia, these clusters are changed and rearranged, depending on the degree of cellular differentiation of the CRC. Using two way ANOVA analysis it was evident that a common feature shared by all cell line, triggered by hypoxia was the significant (p<0,001) downregulation of two specific lipid classes phosphatidylcholines and sphingomyelins. With respect to the lipid composition of the four investigated CRC, we found that hypoxia caused an upregulation in dihydroceramides, in all four cases. In particular, SW480 and LS174T showed an upregulation in all ceramide-related lipid classes, which could be associated with specific regulation of ceramide metabolism of these cell lines under hypoxia.
CONCLUSIONS: The lipid profile of CRC cell lines during a 24 hours hypoxia was described. It shows that hypoxia induces clear changes in lipid classes’ concentration and composition. Particularly, SW480 and LS174 cell lines showed changes in ceramide metabolism induced by hypoxia.
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= Translation stage.
= Clinically available.
