Labeling Cancer Stem Cells with 13C6 Glucose and 13C5 Glutamine for Metabolic Flux Analysis

Methods Mol Biol. 2019:1996:207-216. doi: 10.1007/978-1-4939-9488-5_18.

Abstract

Cancer stem cells (CSCs) or tumor-initiating cells (TICs) are a population of cells present within tumor that have increased self-renewal, chemoresistance, and aggressiveness, thereby contributing to tumor relapse. Literature shows that CSCs or TICs typically originate within the hypoxic niches of the tumor, making hypoxia one of the driving factors for generation of this population. Hypoxic stress promotes adaptation to low oxygen tension in the tissues by altering metabolic properties of the CSCs. This leads to a number of altered enzymatic activities in the CSC population that further contribute to the survival of the CSCs leading to resistance to standard therapy. Hence, understanding this altered metabolic pathways as well as targeting key nodes in these may pave the way for cancer management.Glucose and glutamine are the major substrates utilized by cancer cells and feed into multiple biosynthetic pathways. Hence, labeling and tracking these compounds may reveal some novel metabolic pathways exploited by cancer stem cells to acquire survival advantage. In these current book chapters, we elaborately summarized the basic steps required for isolation, characterization, and metabolic labeling (13C6 glucose and 13C5 glutamine) of CSC for flux analysis.

Keywords: CD133; Cancer stem cells; Hypoxia; Isotope labeling; Metabolic flux.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Carbon Isotopes / chemistry
  • Carbon Isotopes / isolation & purification
  • Cell Hypoxia / drug effects
  • Cell Line, Tumor
  • Cell Separation / methods
  • Disease Models, Animal
  • Glucose / chemistry
  • Glucose / isolation & purification
  • Glucose / metabolism
  • Glutamine / chemistry
  • Glutamine / isolation & purification
  • Glutamine / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
  • Isotope Labeling / methods*
  • Metabolic Flux Analysis / methods*
  • Metabolic Networks and Pathways / drug effects
  • Metabolomics / methods*
  • Mice
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*
  • Pancreatic Neoplasms / pathology
  • Single-Cell Analysis / methods

Substances

  • Antineoplastic Agents
  • Carbon Isotopes
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Glutamine
  • Carbon-13
  • Glucose