Gene expression signatures of breast cancer stem and progenitor cells do not exhibit features of Warburg metabolism

Nicole Gordon, Amy Skinner, Rodney Pommier, Robynn V. Schillace, Steven O'Neill, Jennifer L. Peckham, Patrick Muller, Mary E. Condron, Cory Donovan, Arpana Naik, Juliana Hansen, Su Ellen Johnson Pommier

    Research output: Contribution to journalArticle

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    Abstract

    Introduction: Cancers are believed to adapt to continual changes in glucose and oxygen availability by relying almost exclusively on glycolytic metabolism for energy (i.e. the Warburg effect). The process by which breast cancers sustain growth in avascular tissue is thought to be mediated via aberrant hypoxia response with ensuing shifts in glycolytic metabolism. Given their role in initiating and perpetuating tumors, we sought to determine whether breast cancer stem and progenitor cells play an instrumental role in this adaptive metabolic response. Methods: Breast cancer stem/progenitor cells were isolated from invasive ductal carcinomas, and benign stem cells (SC) were isolated from reduction mammoplasty tissues. Relative expression of 33 genes involved in hypoxia and glucose metabolism was evaluated in flow cytometrically isolated stem and progenitor cell populations. Significance between cohorts and cell populations was determined using Student's 2-tailed t test. Results: While benign stem/progenitor cells exhibited few significant inter-group differences in expression of genes involved in hypoxia regulation or glucose metabolism, breast cancer stem/progenitor cells demonstrated significant inter-group variability. Breast cancer stem/progenitor cells adapted to microenvironments through changes in stem cell numbers and transcription of glycolytic genes. One of four breast cancer stem/progenitor cells subpopulations exhibited an aerobic glycolysis gene expression signature. This subpopulation comprises the majority of the tumor and therefore best reflects invasive ductal carcinoma tumor biology. Although PI3K/AKT mutations are associated with increased proliferation of breast cancer cells, mutations in breast cancer stem/progenitor cells subpopulations did not correlate with changes in metabolic gene expression. Conclusions: The adaptive capacity of breast cancer stem/progenitor cells may enable tumors to survive variable conditions encountered during progressive stages of cancer growth.

    Original languageEnglish (US)
    Article number157
    JournalStem Cell Research and Therapy
    Volume6
    Issue number1
    DOIs
    StatePublished - Aug 28 2015

    Fingerprint

    Neoplastic Stem Cells
    Stem cells
    Transcriptome
    Metabolism
    Gene expression
    Stem Cells
    Breast Neoplasms
    Tumors
    Genes
    Cells
    Glucose
    Neoplasms
    Ductal Carcinoma
    Tissue
    Gene Expression
    Transcription
    Phosphatidylinositol 3-Kinases
    Mutation
    Mammaplasty
    Glycolysis

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology (miscellaneous)
    • Molecular Medicine
    • Cell Biology
    • Medicine (miscellaneous)

    Cite this

    Gene expression signatures of breast cancer stem and progenitor cells do not exhibit features of Warburg metabolism. / Gordon, Nicole; Skinner, Amy; Pommier, Rodney; Schillace, Robynn V.; O'Neill, Steven; Peckham, Jennifer L.; Muller, Patrick; Condron, Mary E.; Donovan, Cory; Naik, Arpana; Hansen, Juliana; Pommier, Su Ellen Johnson.

    In: Stem Cell Research and Therapy, Vol. 6, No. 1, 157, 28.08.2015.

    Research output: Contribution to journalArticle

    Gordon, Nicole ; Skinner, Amy ; Pommier, Rodney ; Schillace, Robynn V. ; O'Neill, Steven ; Peckham, Jennifer L. ; Muller, Patrick ; Condron, Mary E. ; Donovan, Cory ; Naik, Arpana ; Hansen, Juliana ; Pommier, Su Ellen Johnson. / Gene expression signatures of breast cancer stem and progenitor cells do not exhibit features of Warburg metabolism. In: Stem Cell Research and Therapy. 2015 ; Vol. 6, No. 1.
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    abstract = "Introduction: Cancers are believed to adapt to continual changes in glucose and oxygen availability by relying almost exclusively on glycolytic metabolism for energy (i.e. the Warburg effect). The process by which breast cancers sustain growth in avascular tissue is thought to be mediated via aberrant hypoxia response with ensuing shifts in glycolytic metabolism. Given their role in initiating and perpetuating tumors, we sought to determine whether breast cancer stem and progenitor cells play an instrumental role in this adaptive metabolic response. Methods: Breast cancer stem/progenitor cells were isolated from invasive ductal carcinomas, and benign stem cells (SC) were isolated from reduction mammoplasty tissues. Relative expression of 33 genes involved in hypoxia and glucose metabolism was evaluated in flow cytometrically isolated stem and progenitor cell populations. Significance between cohorts and cell populations was determined using Student's 2-tailed t test. Results: While benign stem/progenitor cells exhibited few significant inter-group differences in expression of genes involved in hypoxia regulation or glucose metabolism, breast cancer stem/progenitor cells demonstrated significant inter-group variability. Breast cancer stem/progenitor cells adapted to microenvironments through changes in stem cell numbers and transcription of glycolytic genes. One of four breast cancer stem/progenitor cells subpopulations exhibited an aerobic glycolysis gene expression signature. This subpopulation comprises the majority of the tumor and therefore best reflects invasive ductal carcinoma tumor biology. Although PI3K/AKT mutations are associated with increased proliferation of breast cancer cells, mutations in breast cancer stem/progenitor cells subpopulations did not correlate with changes in metabolic gene expression. Conclusions: The adaptive capacity of breast cancer stem/progenitor cells may enable tumors to survive variable conditions encountered during progressive stages of cancer growth.",
    author = "Nicole Gordon and Amy Skinner and Rodney Pommier and Schillace, {Robynn V.} and Steven O'Neill and Peckham, {Jennifer L.} and Patrick Muller and Condron, {Mary E.} and Cory Donovan and Arpana Naik and Juliana Hansen and Pommier, {Su Ellen Johnson}",
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    T1 - Gene expression signatures of breast cancer stem and progenitor cells do not exhibit features of Warburg metabolism

    AU - Gordon, Nicole

    AU - Skinner, Amy

    AU - Pommier, Rodney

    AU - Schillace, Robynn V.

    AU - O'Neill, Steven

    AU - Peckham, Jennifer L.

    AU - Muller, Patrick

    AU - Condron, Mary E.

    AU - Donovan, Cory

    AU - Naik, Arpana

    AU - Hansen, Juliana

    AU - Pommier, Su Ellen Johnson

    PY - 2015/8/28

    Y1 - 2015/8/28

    N2 - Introduction: Cancers are believed to adapt to continual changes in glucose and oxygen availability by relying almost exclusively on glycolytic metabolism for energy (i.e. the Warburg effect). The process by which breast cancers sustain growth in avascular tissue is thought to be mediated via aberrant hypoxia response with ensuing shifts in glycolytic metabolism. Given their role in initiating and perpetuating tumors, we sought to determine whether breast cancer stem and progenitor cells play an instrumental role in this adaptive metabolic response. Methods: Breast cancer stem/progenitor cells were isolated from invasive ductal carcinomas, and benign stem cells (SC) were isolated from reduction mammoplasty tissues. Relative expression of 33 genes involved in hypoxia and glucose metabolism was evaluated in flow cytometrically isolated stem and progenitor cell populations. Significance between cohorts and cell populations was determined using Student's 2-tailed t test. Results: While benign stem/progenitor cells exhibited few significant inter-group differences in expression of genes involved in hypoxia regulation or glucose metabolism, breast cancer stem/progenitor cells demonstrated significant inter-group variability. Breast cancer stem/progenitor cells adapted to microenvironments through changes in stem cell numbers and transcription of glycolytic genes. One of four breast cancer stem/progenitor cells subpopulations exhibited an aerobic glycolysis gene expression signature. This subpopulation comprises the majority of the tumor and therefore best reflects invasive ductal carcinoma tumor biology. Although PI3K/AKT mutations are associated with increased proliferation of breast cancer cells, mutations in breast cancer stem/progenitor cells subpopulations did not correlate with changes in metabolic gene expression. Conclusions: The adaptive capacity of breast cancer stem/progenitor cells may enable tumors to survive variable conditions encountered during progressive stages of cancer growth.

    AB - Introduction: Cancers are believed to adapt to continual changes in glucose and oxygen availability by relying almost exclusively on glycolytic metabolism for energy (i.e. the Warburg effect). The process by which breast cancers sustain growth in avascular tissue is thought to be mediated via aberrant hypoxia response with ensuing shifts in glycolytic metabolism. Given their role in initiating and perpetuating tumors, we sought to determine whether breast cancer stem and progenitor cells play an instrumental role in this adaptive metabolic response. Methods: Breast cancer stem/progenitor cells were isolated from invasive ductal carcinomas, and benign stem cells (SC) were isolated from reduction mammoplasty tissues. Relative expression of 33 genes involved in hypoxia and glucose metabolism was evaluated in flow cytometrically isolated stem and progenitor cell populations. Significance between cohorts and cell populations was determined using Student's 2-tailed t test. Results: While benign stem/progenitor cells exhibited few significant inter-group differences in expression of genes involved in hypoxia regulation or glucose metabolism, breast cancer stem/progenitor cells demonstrated significant inter-group variability. Breast cancer stem/progenitor cells adapted to microenvironments through changes in stem cell numbers and transcription of glycolytic genes. One of four breast cancer stem/progenitor cells subpopulations exhibited an aerobic glycolysis gene expression signature. This subpopulation comprises the majority of the tumor and therefore best reflects invasive ductal carcinoma tumor biology. Although PI3K/AKT mutations are associated with increased proliferation of breast cancer cells, mutations in breast cancer stem/progenitor cells subpopulations did not correlate with changes in metabolic gene expression. Conclusions: The adaptive capacity of breast cancer stem/progenitor cells may enable tumors to survive variable conditions encountered during progressive stages of cancer growth.

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