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Tracking Functional Tumor Cell Subpopulations of Malignant Glioma by Phasor Fluorescence Lifetime Imaging Microscopy of NADH.
Trinh, Andrew L; Chen, Hongtao; Chen, Yumay; Hu, Yuanjie; Li, Zhenzhi; Siegel, Eric R; Linskey, Mark E; Wang, Ping H; Digman, Michelle A; Zhou, Yi-Hong.
Afiliación
  • Trinh AL; Laboratory for Fluorescence Dynamics and Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA. atrinh2@uci.edu.
  • Chen H; Laboratory for Fluorescence Dynamics and Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA. hchenuci@gmail.com.
  • Chen Y; UC Irvine Diabetes Center and Department of Medicine, University of California, Irvine, CA 92697, USA. yumayc@uci.edu.
  • Hu Y; UC Irvine Brain Tumor Laboratory and Department of Surgery, University of California, Irvine, CA 92697, USA. yuanjieh@uci.edu.
  • Li Z; UC Irvine Brain Tumor Laboratory and Department of Surgery, University of California, Irvine, CA 92697, USA. zzrickli@gmail.com.
  • Siegel ER; Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. SiegelEricR@uams.edu.
  • Linskey ME; UC Irvine Brain Tumor Laboratory and Department of Surgery, University of California, Irvine, CA 92697, USA. mlinskey@uci.edu.
  • Wang PH; UC Irvine Diabetes Center and Department of Medicine, University of California, Irvine, CA 92697, USA. phwang@uci.edu.
  • Digman MA; Laboratory for Fluorescence Dynamics and Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA. mdigman@uci.edu.
  • Zhou YH; UC Irvine Brain Tumor Laboratory and Department of Surgery, University of California, Irvine, CA 92697, USA. yihongz@uci.edu.
Cancers (Basel) ; 9(12)2017 Dec 06.
Article en En | MEDLINE | ID: mdl-29211022
Intra-tumoral heterogeneity is associated with therapeutic resistance of cancer and there exists a need to non-invasively identify functional tumor subpopulations responsible for tumor recurrence. Reduced nicotinamide adenine dinucleotide (NADH) is a metabolic coenzyme essential in cellular respiration. Fluorescence lifetime imaging microscopy (FLIM) of NADH has been demonstrated to be a powerful label-free indicator for inferring metabolic states of living cells. Using FLIM, we identified a significant shift towards longer NADH fluorescence lifetimes, suggesting an increase in the fraction of protein-bound NADH, in the invasive stem-like tumor-initiating cell (STIC) subpopulation relative to the tumor mass-forming cell (TMC) subpopulation of malignant gliomas. By applying our previously studied model to transition glioma from a majority of STIC to a majority of TMC in serum-adherent culture conditions following serial passages, we compared changes in NADH states, cellular respirations (oxidative phosphorylation and glycolysis), EGFR expression, and cell-growth speed over passages. We identified a significant positive correlation between free-NADH fraction and cell growth, which was related to an increase of TMC fraction. In comparison, the increase of EGFR and cellular respirations preceded all these changes. In conclusion, FLIM of NADH provides a non-invasive method to monitor the dynamics of tumor heterogeneity before and after treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza