Gasinska A.,Zakiad Radiobiologii Klinicznej |
Janecka A.,Zakiad Radiobiologii Klinicznej |
Adamczyk A.,Zakiad Radiobiologii Klinicznej |
Slonina D.,Zakiad Radiobiologii Klinicznej
Nowotwory | Year: 2013
Otto Warburg at the beginning of the 20th century suggested that cancer cells exhibit different metabolism than normal cells. He demonstrated that tumour cells prefer aerobic glycolisis rather than oxidative respiration as for normal cells. They convert large amounts of glucose to lactate in the process of glycolysis, and even in the presence of oxygen. The phenomenon is known as the Warburg effect or aerobic glycolysis. The biochemist hypothesized that the cause of this is mitochondrial damage in tumour cells. The reason why cells undergo the Warburg effect is still poorly understood. However it is known that many proliferating cells, also malignant cells, show increased uptake of glucose and restriction of oxidative phosphorylation. This metabolic pathway facilitates high levels of lactate production, even in the presence of oxygen. Recent evidence suggests that metabolites themselves can be oncogenic by altering cell © Polskie Towarzystwo Onkologiczne ISSN 0029-540X www.nowotwory.viamedica.pl signaling and blocking cellular differentiation. These changes facilitate the process of oncogenesis and cell growth. The pyruvate kinase (PK), a glycolitic enzyme is replaced by isoform of PKM2 which facilitates aerobic glycolisis in cancer cells. PKM2 is also a regulator of cellular anti-oxidative metabolism which promotes cancer growth by activating pentose phosphate pathway, maintaining the balance of redox equivalents and activating antioxidant defence system. Recently there has been proposed a new model of cancer metabolism, which has been proved experimentally, termed reverse Warburg effect.This model explains the role of aerobic glycolysis and lactate production in fueling tumour growth. This model assumes metabolic cooperation between stromal fibroblasts and tumour cells, and that cancer cells perform oxidative respiration. In activated fibroblasts, oxidative stress in the tumour microenvironment leads to authophagy, mitophagy and aerobic glycolysis, which delivers high-energetic intermediates such as lactate, ketones and glutamine to tumour cells that fuel the anabolic growth. Tumour cells due to delivered nutrients can lead anabolic metabolism and produce high amounts of ATP what facilitates tumour growth, development and progression.