Effects of extracellular modulation through hypoxia on the glucose metabolism of human breast cancer stem cells

1st Physics and Technologies in Medicine and Dentistry Symposium

物理学;医药卫生

Yustisia, I.^1 ; Jusman, S.W.A.^2 ; Wanandi, S.I.^2

Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia^1

Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia^2

关键词: Cancer stem cells;    Enzymatic reaction;    Extracellular environments;    Extracellular pH;    Glucose consumption;    Glucose metabolism;    Human breast cancer;    Incubation periods;   

Others  :  https://iopscience.iop.org/article/10.1088/1742-6596/884/1/012026/pdf
DOI  :  10.1088/1742-6596/884/1/012026

学科分类：卫生学

来源: IOP

【 摘 要 】

Cancer stem cells have been reported to maintain stemness under certain extracellular changes. This study aimed to analyze the effect of extracellular O2level modulation on the glucose metabolism of human CD24-/CD44+ breast cancer stem cells (BCSCs). The primary BCSCs (CD24-/CD44+ cells) were cultured under hypoxia (1% O2) for 0.5, 4, 6, 24 and 48 hours. After each incubation period, HIF1α, GLUT1 and CA9 expressions, as well as glucose metabolism status, including glucose consumption, lactate production, O2consumption and extracellular pH (pHe) were analyzed using qRT-PCR, colorimetry, fluorometry, and enzymatic reactions, respectively. Hypoxia caused an increase in HIF1α mRNA expressions and protein levels and shifted the metabolic states to anaerobic glycolysis, as demonstrated by increased glucose consumption and lactate production, as well as decreased O2consumption and pHe. Furthermore, we demonstrated that GLUT1 and CA9 mRNA expressions simultaneously increased, in line with HIF1α expression. In conclusion, modulation of the extracellular environment of human BCSCs through hypoxia shifedt the metabolic state of BCSCs to anaerobic glycolysis, which might be associated with GLUT1 and CA9 expressions regulated by HIFlα transcription factor.