Li Junjie, Condello Salvatore, Thomes-Pepin Jessica, Ma Xiaoxiao, Xia Yu, Hurley Thomas D, Matei Daniela, Cheng Ji-Xin
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Cell Stem Cell. 2017 Mar 2;20(3):303-314.e5. doi: 10.1016/j.stem.2016.11.004. Epub 2016 Dec 29.
Lack of sensitive single-cell analysis tools has limited the characterization of metabolic activity in cancer stem cells. By hyperspectral-stimulated Raman scattering imaging of single living cells and mass spectrometry analysis of extracted lipids, we report here significantly increased levels of unsaturated lipids in ovarian cancer stem cells (CSCs) as compared to non-CSCs. Higher lipid unsaturation levels were also detected in CSC-enriched spheroids compared to monolayer cultures of ovarian cancer cell lines or primary cells. Inhibition of lipid desaturases effectively eliminated CSCs, suppressed sphere formation in vitro, and blocked tumor initiation capacity in vivo. Mechanistically, we demonstrate that nuclear factor κB (NF-κB) directly regulates the expression levels of lipid desaturases, and inhibition of desaturases blocks NF-κB signaling. Collectively, our findings reveal that increased lipid unsaturation is a metabolic marker for ovarian CSCs and a target for CSC-specific therapy.
缺乏灵敏的单细胞分析工具限制了对癌症干细胞代谢活性的表征。通过对单个活细胞进行高光谱刺激拉曼散射成像以及对提取的脂质进行质谱分析，我们在此报告，与非癌症干细胞相比，卵巢癌干细胞（CSCs）中不饱和脂质水平显著升高。与卵巢癌细胞系或原代细胞的单层培养相比，在富含CSCs的球体中也检测到更高的脂质不饱和水平。抑制脂质去饱和酶可有效消除CSCs，在体外抑制球体形成，并在体内阻断肿瘤起始能力。从机制上讲，我们证明核因子κB（NF-κB）直接调节脂质去饱和酶的表达水平，而去饱和酶的抑制会阻断NF-κB信号传导。总体而言，我们的研究结果表明，脂质不饱和增加是卵巢CSCs的代谢标志物和CSC特异性治疗的靶点。
