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Metabolic profiles of cancer cells

Nature Reviews Cancer volume 4, pages 551–561 (2004)Cite this article

Key Points

  • Metabolomics is the study of the complete metabolic compliment of the cell, organ or organism.

  • The technique involves the combined use of multivariate statistics and an analytical technique such as nuclear magnetic resonance spectroscopy, gas chromatography–mass spectrometry or liquid chromatography–mass spectrometry.

  • A wide range of metabolites have been shown to be useful in distinguishing tumours from healthy tissue and in monitoring cellular activities such as cell-cycle progression or apoptosis.

  • Metabolomic approaches have been used to study the function of hypoxia-inducible factor 1 in tumour growth and shown that this transcription factor is involved in increasing glucose metabolism, rather than inducing angiogenesis, in hepatomas.

  • In vivo studies have shown that magnetic resonance spectroscopy can be used to identify tumour types, especially brain tumours, by their metabolic profiles.

  • As both nuclear magnetic resonance spectroscopy and mass spectrometry are high-throughput technologies, these tools can be used to profile systemic metabolism in tumour diagnosis and prognosis, through analysis of urine and blood plasma.

Abstract

In the post-genomic era, several profiling tools have been developed to provide a more comprehensive picture of tumour development and progression. The global analysis of metabolites, such as by mass spectrometry and high-resolution 1H nuclear magnetic resonance spectroscopy, can be used to define the metabolic phenotype of cells, tissues or organisms. These 'metabolomic' approaches are providing important information about tumorigenesis, revealing new therapeutic targets and will be an important component of automated diagnosis.

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Figure 1: The biological organization of the '-omes'.
Figure 2: An in vivo, in vitro and in situ study of apoptosis in tumours.
Figure 3: Monitoring the action of tamoxifen on endometrial cells.

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Acknowledgements

J.L.G. is supported by a Royal Society University Fellowship. The authors would like to thank R. Kauppinen of the University of Manchester, UK, and H. Antti of the University of Umea, Sweden, for supplying figures.

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Authors and Affiliations

  1. Department of Biochemistry, University of Cambridge, Tennis Court Road, CB2 1GA, UK

    Julian L. Griffin

  2. Bruker Biospin, 15 Fortune Drive, Billerica, 01821, Massachusetts, USA

    John P. Shockcor

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DATABASES

Cancer.gov

brain cancer

breast cancer

cervical cancer

chronic lymphocytic leukaemia

colon cancer

Entrez Gene

GLUT1

GLUT3

HIF-1α

HIF-1β

VEGF

FURTHER INFORMATION

International Network for Pattern Recognition of Tumours Using Magnetic Resonance

Metabometrix glossary

Plant metabolmics

SpectroscopyNOW

Glossary

T2 RELAXATION MEASUREMENTS

The nuclear magnetic resonance (NMR) signal decays by several physical processes, one of which is T2 relaxation. This rate of relaxation is faster for metabolites that are slowly moving in the cell. NMR analysis can exploit this property, to selectively detect fast-tumbling molecules, which include many of the metabolites that are found in the cytosol. These spectra are referred to as 'T2 weighted'.

LINE WIDTHS

The distance between the two sides of a NMR signal (resonance) at the half height of the resonance. Each resonance will have a line width that is inversely dependent on the rate of T2 relaxation for that resonance. Therefore, metabolites that are slowly moving have broad line widths.

SPINNING RATE

During high-resolution magic angle spinning 1H nuclear magnetic resonance spectroscopy experiments samples are spun at an angle (the so-called magic angle) to the magnetic field to reduce line-broadening effects.

TUNEL STAINING

(Terminal deoxynucleotidyl transferase-mediated dUTP nick and labelling). A procedure for identifying apoptotic cells based on the detection of DNA cleavage.

NEURAL NETWORKS

Pattern-recognition processes that iteratively search for the best solution using a network construction that is similar to neurones in the brain.

CO-RESONANT METABOLITES

Nuclear magnetic resonance (NMR) spectroscopy detects the chemical groups that make up a molecule. Some metabolites have regions that are chemically very similar and therefore occur in the same position in the NMR spectrum. When the individual peaks (resonances) from two or more metabolites can not be distinguished, they are said to be 'co-resonant'. This confounds direct quantification.

FOURIER-TRANSFORM INFRARED SPECTROSCOPY

Spectroscopic technique based on examining the vibrational frequencies of given molecules. When a molecule absorbs infrared radiation of a defined energy, vibrations are induced in the molecule. However, these vibrations must involve an electrical dipolar change in the molecule. In general, this technique is poor at discriminating metabolites from a similar class of compounds.

RAMAN SPECTROSCOPY

When a metabolite is irradiated by light from a laser, the light is scattered with either the same amount of energy (Rayleigh scattering), or with more (Stokes) or less (anti-Stokes) energy because of changes in the vibrational energy of the metabolite. This Stokes and anti-Stokes scattering is observed in Raman spectroscopy.

CRYOPROBE

Nuclear magnetic resonance (NMR) probes for which the coil and pre-amplifier have been cryogenically cooled to reduce the amount of electronic noise in the NMR signal. They increase the signal-to-noise ratio by a factor of 3–4, compared with conventional probes. This can reduce experiment time 16-fold or required sample concentration by up to 4-fold.

LARMOR FREQUENCY

When a magnet or dipole is placed in a magnetic field, a torque is placed on it, called a 'magnetic moment', causing it to align with the magnetic field. For an electron, however, the magnetic moment is produced by the orbital motion of the electron about the nucleus. This produces a force that causes the magnetic moment to process around the direction of the magnetic field at a frequency termed the Larmor frequency.

PENTOSE-PHOSPHATE PATHWAY

An anabolic pathway that uses the six carbons of glucose to generate five-carbon sugars. The roles of this pathway are to generate NADPH for biosynthesis reactions, to provide cells with ribose-5-phosphate for nucleotide synthesis and to metabolize pentose sugars.

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Griffin, J., Shockcor, J. Metabolic profiles of cancer cells. Nat Rev Cancer 4, 551–561 (2004). https://doi.org/10.1038/nrc1390

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