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LIPIDOMIC PROFILING OF COLORECTAL CANCER (CRC) CELL LINES UNDER HYPOXIA Alarcon-Barrera, J.C .1,2 , Steenvoorden E. 1 , Oleg A Mayboroda 1 , A. Ondo-Mendez 2 , Giera, M. 1 1 Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), Leiden, The Netherlands 2 Universidad del Rosario, Escuela de Medicina y Ciencias de la Salud, Bogotá, Colombia. Do exist common features in the lipid profile of different CRC cell lines under hypoxia? BACKGROUND CRC is a disease with multiple stages and grades depending on the location and cell differentiation status. During CRC development, the tumor microenvironment (TM) has shown to be a key component to sustain progress and spreading of the tumor . Hypoxia is a well-known state during tumor development, it is responsible for metabolic adaptation, and lipid re-modeling . Intrinsic heterogeneity of CRC and TM highlights the importance of studying hypoxia across different CRC cell lines to a better understand cancer and tumor microenvironment biology. METHODOLOGY HT29 LS174T SW480 HCT116 - Lipid Classes - Fatty Acids - Lipid Species RESULTS Fig 1. Lipid profiling of CRC cell lines in normoxia A) and hypoxia B). Analysis of the lipid class composition in the basal state (normoxia) revealed that mostly differences are in ceramide metabolism; on the other side major cell components are membrane lipids. Clustering analysis showed alterations in the lipid profile upon hypoxia treatment. Ceramide – related, LPE, and LPC lipid classes were the most evident changes A Fig 2. Common lipid classes up or down regulated after hypoxia. Volcano plot analysis for each individual cell line displayed upregulation of DCER, and down regulation of SM lipid classes, as a common feature after hypoxia. Moreover, SW480 and LS174T shared changes in lipid classes related with ceramide metabolism. Fig 3. Fatty acid composition in lipid classes affected by hypoxia. Lipid classes, previously shown to be up or down regulated, were analyzed at the fatty acid composition level. Results showed HT29 and LST174T to be less hypoxia responsive compared to the other two cell lines, however, the four cell lines shared an upregulation in long and very long saturated fatty acid from DCER lipid classes. CONCLUSION Hypoxia induces changes in the lipid metabolism of CRC cell lines that are mainly associated to long and very long fatty acids from DCER lipid class. Contact info: Juan Carlos Alarcon Barrera [email protected] 1% O 2 # 4c B LS174T SW480 HCT116 HT29 log2 (FC) -log10(p) -0.8 -0.6 -0.4 -0.2 0.0 0.2 0 2 4 6 8 HCT116 Difference -log(q value) CE CER DAG DCER FFA HCER LCER LPC LPE PC PE SM TAG -0.2 0.0 0.2 0.4 0.6 0.0 0.5 1.0 1.5 2.0 2.5 HT29 -log(q value) CE CER DAG DCER FFA HCER LCER LPC LPE PC PE SM TAG -0.3 -0.2 -0.1 0.0 0.1 0 2 4 6 LS174T -log(q value) CE CER DAG DCER FFA HCER LCER LPC LPE PC PE SM TAG -0.6 -0.4 -0.2 0.0 0.2 0 2 4 6 8 10 SW480 Difference -log(q value) CE CER DAG DCER FFA HCER LCER LPC LPE PC PE SM TAG

PowerPoint Presentation · 2019. 9. 3. · Title: PowerPoint Presentation Author: ��Alarc�n Barrera, J.C. (CPM) Created Date: 9/3/2019 11:34:14 AM

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  • LIPIDOMIC PROFILING OF COLORECTAL CANCER (CRC) CELL LINES UNDER HYPOXIA

    Alarcon-Barrera, J.C.1,2, Steenvoorden E. 1, Oleg A Mayboroda 1, A. Ondo-Mendez2, Giera, M. 11Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), Leiden, The Netherlands

    2Universidad del Rosario, Escuela de Medicina y Ciencias de la Salud, Bogotá, Colombia.

    Do exist common features in the lipid profile of different CRC cell lines under hypoxia?

    BACKGROUND➢ CRC is a disease with multiple stages and grades depending on

    the location and cell differentiation status.➢ During CRC development, the tumor microenvironment (TM)

    has shown to be a key component to sustain progress andspreading of the tumor .

    ➢ Hypoxia is a well-known state during tumor development, it isresponsible for metabolic adaptation, and lipid re-modeling .

    ➢ Intrinsic heterogeneity of CRC and TM highlights the importanceof studying hypoxia across different CRC cell lines to a betterunderstand cancer and tumor microenvironment biology.

    METHODOLOGY

    HT29LS174TSW480HCT116

    -Lipid Classes -Fatty Acids-Lipid Species

    RESULTS

    Fig 1. Lipid profiling of CRC cell lines in normoxia A) and hypoxiaB). Analysis of the lipid class composition in the basal state(normoxia) revealed that mostly differences are in ceramidemetabolism; on the other side major cell components aremembrane lipids. Clustering analysis showed alterations in thelipid profile upon hypoxia treatment. Ceramide – related, LPE, andLPC lipid classes were the most evident changes

    A

    Fig 2. Common lipid classes up or down regulated after hypoxia.Volcano plot analysis for each individual cell line displayedupregulation of DCER, and down regulation of SM lipid classes, asa common feature after hypoxia. Moreover, SW480 and LS174Tshared changes in lipid classes related with ceramide metabolism.

    Fig 3. Fatty acid composition in lipid classes affected by hypoxia. Lipid classes, previously shown to be up or down regulated, wereanalyzed at the fatty acid composition level. Results showed HT29 and LST174T to be less hypoxia responsive compared to the othertwo cell lines, however, the four cell lines shared an upregulation in long and very long saturated fatty acid from DCER lipid classes.

    CONCLUSIONHypoxia induces changes in the lipid metabolism of CRC cell lines that are mainly associated to

    long and very long fatty acids from DCER lipid class.

    Contact info:

    Juan Carlos Alarcon Barrera

    [email protected]

    1% O2

    # 4c

    B

    LS174T SW480HCT116HT29

    log2 (FC)

    -lo

    g10

    (p)

    -0.8 -0.6 -0.4 -0.2 0.0 0.20

    2

    4

    6

    8 HCT116

    Difference

    -lo

    g(q

    valu

    e)

    CE

    CER

    DAG

    DCER

    FFAHCER

    LCER

    LPCLPE

    PC

    PE

    SMTAG

    -0.2 0.0 0.2 0.4 0.60.0

    0.5

    1.0

    1.5

    2.0

    2.5 HT29

    -lo

    g(q

    valu

    e)

    CE

    CER

    DAG

    DCER

    FFA

    HCERLCER

    LPC

    LPE

    PC

    PE

    SM

    TAG

    -0.3 -0.2 -0.1 0.0 0.10

    2

    4

    6 LS174T

    -lo

    g(q

    valu

    e)

    CE

    CER

    DAG

    DCER

    FFA

    HCERLCER

    LPCLPE

    PC

    PE

    SM

    TAG

    -0.6 -0.4 -0.2 0.0 0.20

    2

    4

    6

    8

    10SW480

    Difference

    -lo

    g(q

    valu

    e)

    CE CER

    DAG

    DCER

    FFA

    HCERLCER

    LPCLPE PC

    PE

    SM

    TAG