Acid production in glycolysis-impaired tumors provides new insights into tumor metabolism

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Publication Details

Author list: Sckell A
Publisher: American Association for Cancer Research
Publication year: 2002
Volume number: 8
Issue number: 4
Start page: 1284
End page: 1291
Number of pages: 8
ISSN: 1078-0432
Languages: English-Great Britain (EN-GB)


Abstract

Purpose: Low extracellular pH is a hallmark of solid tumors. It has long
been thought that this acidity is mainly attributable to the production
of lactic acid. In this study, we tested the hypothesis that lactate is
not the only source of acidification in solid tumors and explored the
potential mechanisms underlying these often-observed high rates of acid
production. Experimental Design: We compared the metabolic profiles of
glycolysis-impaired (phosphoglucose isomerase-deficient) and parental
cells in both in vitro and two in vivo models (dorsal skinfold chamber
and Gullino chamber). Results: We demonstrated that CO2, in
addition to lactic acid, was a significant source of acidity in tumors.
We also found evidence supporting the hypothesis that tumor cells rely
on glutaminolysis for energy production and that the pentose phosphate
pathway is highly active within tumor cells. Our results also suggest
that the tricarboxylic acid cycle is saturable and that different
metabolic pathways are activated to provide for energy production and
biosynthesis. Conclusions: These results are consistent with the
paradigm that tumor metabolism is determined mainly by substrate
availability and not by the metabolic demand of tumor cells per se. In
particular, it appears that the local glucose and oxygen availabilities
each independently affect tumor acidity. These findings have significant
implications for cancer treatment.


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Neuroscience


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Last updated on 2019-10-08 at 00:15