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Adaptive alterations in cellular metabolism with malignant transformation
C P Fischer1, B P Bode, W W Souba
1Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
Annals of Surgery
|May 30, 1998
Summary
Malignant transformation increases glutamine transport and shifts nutrient utilization from glutamine oxidation to glucose oxidation in fibrosarcoma cells. This metabolic reprogramming supports protein synthesis, not just cell growth.
Area of Science:
- Cellular metabolism
- Cancer biology
- Molecular oncology
Background:
- Malignant transformation necessitates efficient nutrient utilization for energy, synthesis, and division.
- Cancer cells rely heavily on glucose and glutamine for energy and biosynthesis.
- Glutamine is crucial for protein and DNA synthesis in rapidly dividing cells.
Purpose of the Study:
- To investigate differential glutamine and glucose utilization between normal fibroblasts and fibrosarcoma cells.
- To understand metabolic alterations during malignant transformation.
- To elucidate the role of nutrient metabolism in cancer development.
Main Methods:
- Comparative analysis of glutamine and glucose metabolism in normal rat kidney fibroblasts and rat fibrosarcoma cells.
- Measurement of glutamine transport, glutaminase activity, and oxidation rates to CO2.
- Assessment of protein synthesis from glutamine and glutamine-dependent growth rates.
Main Results:
- Fibrosarcomas exhibited a sixfold increase in glutamine transport via a high-affinity system (ASC).
- Glutamine oxidation to CO2 decreased in fibrosarcomas, with a metabolic shift towards increased glucose oxidation.
- Despite increased nutrient utilization, fibrosarcoma cells showed lower growth rates than normal fibroblasts.
Conclusions:
- Malignant transformation involves enhanced glutamine transport and a switch to glucose as the primary oxidative fuel.
- Glutamine is redirected towards protein synthesis in fibrosarcomas, while glucose fuels energy demands.
- These metabolic changes are linked to the malignant phenotype rather than solely increased cell proliferation.