Warburg effect

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The Warburg effect (after Otto Heinrich Warburg ) is the change in glucose metabolism observed in many cancer cells , through which the cells obtain their energy mainly through glycolysis with subsequent excretion of lactate ( lactic acid fermentation ) instead of the end product of glycolysis like normal cells To supply the citric acid cycle in the mitochondria . This metabolic situation is also shown by healthy cells when there is a lack of oxygen (so-called anaerobic glycolysis). The specialty of the Warburg effect is that cancer cells show this behavior even when there is sufficient oxygen supply, which is why Warburg referred to this as aerobic glycolysis . This type of energy production is very inefficient, which is why the cancer cells affected have an increased consumption of glucose. Why cancer cells still use this way of generating energy is the subject of current cancer research. In 70% of the cancer cases, an overexpression of glycolysis-relevant enzymes and membrane transporters could be demonstrated. Anaerobic glycolysis is not the only source of lactate. Tumor cells can also activate alternative metabolic pathways, such as synthesis from glutamine and alanine . The tumor cells initially have disadvantages due to the change in metabolism, since both anaerobic glycolysis provides less energy and the synthesis of lactic acid from other metabolites requires energy. Pyruvate , lactate, and some other glycolysis-associated metabolites are chemical scavengers . Many tumor therapies , especially ionizing radiation and certain chemotherapeutic agents, work by generating radicals. Tumor cells with many radicals are therefore more difficult to fight. Therefore, the lactate content of clinical tumors is the subject of research. The levels of glucose, lactate and pyruvate can be measured on tissue samples, for example, by means of an induced bioluminescence reaction . An increased lactate level in ENT tumors was linked to an increased risk of metastasis. Otto Warburg's original hypothesis , according to which the Warburg effect is the cause of cancer development, is considered outdated.

literature

Individual evidence

  1. ^ O Warburg, K Posener, E Negelein: not known. In: Biochemical Journal . tape 152 , 1924, pp. 319 .
  2. ^ O Warburg: On the origin of cancer cells . In: Science (New York, NY) . tape 123 , no. 3191 , February 24, 1956, ISSN  0036-8075 , p. 309-314 , doi : 10.1126 / science.123.3191.309 , PMID 13298683 .
  3. ^ B Altenberg, KO Greulich: Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes . In: Genomics . tape 84 , no. 6 , 2004, ISSN  0888-7543 , p. 1014-1020 , doi : 10.1016 / j.ygeno.2004.08.010 , PMID 15533718 .
  4. ^ Matthew G Vander Heiden, Lewis C Cantley, Craig B Thompson: Understanding the Warburg effect: the metabolic requirements of cell proliferation . In: Science (New York, NY) . tape 324 , no. 5930 , May 22, 2009, ISSN  1095-9203 , doi : 10.1126 / science.1160809 , PMID 19460998 , PMC 2849637 (free full text).
  5. ↑ Ulrike GA Sattler, Wolfgang Mueller-Klieser: The anti-oxidant capacity of tumor glycolysis . In: International Journal of Radiation Biology . tape 85 , no. November 11 , 2009, ISSN  1362-3095 , p. 963-971 , doi : 10.3109 / 09553000903258889 , PMID 19895273 .
  6. ↑ David M Brizel, Thies Schroeder, Richard L Scher, Stefan Walenta, Robert W Clough: Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer . In: International Journal of Radiation Oncology * Biology * Physics . tape 51 , no. 2 , 2001, p. 349–353 , doi : 10.1016 / S0360-3016 (01) 01630-3 ( elsevier.com [accessed May 18, 2020]).
  7. ^ Robert Allan Weinberg : The biology of cancer . 2nd Edition. Garland Science, New York 2014. pp. 53 f.