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Stromal-epithelial metabolic coupling in cancer: integrating autophagy and metabolism in the tumor microenvironment.
- Source :
-
The international journal of biochemistry & cell biology [Int J Biochem Cell Biol] 2011 Jul; Vol. 43 (7), pp. 1045-51. Date of Electronic Publication: 2011 Feb 15. - Publication Year :
- 2011
-
Abstract
- Cancer cells do not exist as pure homogeneous populations in vivo. Instead they are embedded in "cancer cell nests" that are surrounded by stromal cells, especially cancer associated fibroblasts. Thus, it is not unreasonable to suspect that stromal fibroblasts could influence the metabolism of adjacent cancer cells, and visa versa. In accordance with this idea, we have recently proposed that the Warburg effect in cancer cells may be due to culturing cancer cells by themselves, out of their normal stromal context or tumor microenvironment. In fact, when cancer cells are co-cultured with fibroblasts, then cancer cells increase their mitochondrial mass, while fibroblasts lose their mitochondria. An in depth analysis of this phenomenon reveals that aggressive cancer cells are "parasites" that use oxidative stress as a "weapon" to extract nutrients from surrounding stromal cells. Oxidative stress in fibroblasts induces the autophagic destruction of mitochondria, by mitophagy. Then, stromal cells are forced to undergo aerobic glycolysis, and produce energy-rich nutrients (such as lactate and ketones) to "feed" cancer cells. This mechanism would allow cancer cells to seed anywhere, without blood vessels as a food source, as they could simply induce oxidative stress wherever they go, explaining how cancer cells survive during metastasis. We suggest that stromal catabolism, via autophagy and mitophagy, fuels the anabolic growth of tumor cells, promoting tumor progression and metastasis. We have previously termed this new paradigm "The Autophagic Tumor Stroma Model of Cancer Metabolism", or the "Reverse Warburg Effect". We also discuss how glutamine addiction (glutaminolysis) in cancer cells fits well with this new model, by promoting oxidative mitochondrial metabolism in aggressive cancer cells.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Autophagy
Biomarkers, Tumor
Cell Hypoxia
Cell Line, Tumor
Coculture Techniques
Female
Glutamine metabolism
Glycolysis
Humans
Mice
Models, Biological
Neoplasms pathology
Oxidative Stress
Reactive Oxygen Species metabolism
Caveolin 1 metabolism
Fibroblasts metabolism
Mitochondria metabolism
Neoplasms metabolism
Stromal Cells metabolism
Tumor Microenvironment physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5875
- Volume :
- 43
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- The international journal of biochemistry & cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 21300172
- Full Text :
- https://doi.org/10.1016/j.biocel.2011.01.023