Cancer Metabolism

 

Imagine if Otto Warburg had an XF Extracellular Flux Analyzer...

In 1931, German biochemist Otto Warburg was awarded the Nobel Prize for his work in understanding cancer metabolism, revealing that cancer cells burn sugar (glycolysis) differently than normal cells, preferring to burn sugar over energy rich fats even when cellualr oxygen conditions favor mitochondrial fat burning. Warburg hypothesized that cancer is caused by mitochondrial dysfunction forcing the cells to use aerobic glycolysis instead of beta oxidation (OXPHOS).

Today, his obeservaton is known as the "Warburg Effect" and is widely accepted as fundamental to Cancer biology. But the belief that it is a mitochondrial defect remains a debate.

Warburg made his discovery with a device of his own design referred to as the "Warburg Apparatus"--a manometer that measures mitochondrial oxygen consumption of cells.

Much easier to use than the Warburg Apparatus, the Seahorse XF Extracellular Flux Analyzer is playing a key role in the current resurgence in research into cancer cell metabolism, the Warburg Effect and drugs that affect it.

The XF Analyzer allows a scientist to measure cancer metabolism in real time, in a microplate. In minutes, the XF Analyzer measures oxygen consumption rate (OCR)--a measure of mitochondrial respiration (fat burning)--as well as extracellular acidification rate (ECAR), a measure of glycolysis (sugar burning).

With just a small number of cells, investigators can measure the affects of up to four compounds on cellular metabolism, determining the basal oxygen consumption and glycolysis rates; respiratory capacity; mitochondrial dysfunction; fatty acid oxidation, uncoupling; ATP turnover; glucose, fatty acid, and amino acid metabolism and cell signaling in primary, adherent, tumor and suspension cells or islets, and isolated mitochondria. All important information needed when developing new drugs.

Studies utilizing the XF are revealing the metabolic dependencies of cancer cells on glucose and potential therapies. Scientists can determine whether a cancer is addicted to glucose or glutamine, and establish which pathway to target for intervention.

 

Maybe he would have discovered this...

Recent Cancer Metabolism Publications

• UOK 262 cell line, fumarate hydratase deficient (FH-/FH-) hereditary leiomyomatosis renal cell carcinoma: in vitro and in vivo model of an aberrant energy metabolic pathway in human cancer.

  Yang Y, Valera VA, Padilla-Nash HM, Sourbier C, Vocke CD, Vira MA, Abu-Asab MS, Bratslavsky G, Tsokos M, Merino MJ, Pinto PA, Srinivasan R, Ried T, Neckers L, Linehan WM.; (2010) Cancer Genet Cytogenet. Jan 1;196(1):45-55.

• Increased OXPHOS activity precedes rise in glycolytic rate in H-RasV12/E1A transformed fibroblasts that develop a Warburg phenotype.

  de Groof AJ, Te Lindert MM, van Dommelen MM, Wu M, Willemse M, Smift AL, Winer M, Oerlemans F, Pluk H, Fransen JA, Wieringa B., (2009) Mol Cancer, Jul 31;8(1):54.

• Hyaluronan, CD44, and Emmprin Regulate Lactate Efflux and Membrane Localization of Monocarboxylate Transporters in Human Breast Carcinoma Cells.

  Slomiany MG, Grass GD, Robertson AD, Yang XY, Maria BL, Beeson C, Toole BP. Cancer Res. 69(4):1293-1301, 2009.

• Multiparameter metabolic analysis reveals a close link between attenuated mitochondrial bioenergetic function and enhanced glycolysis dependency in human tumor cells.

  Wu M, Neilson A, Swift AL, Moran R, Tamagnine J, Parslow D, Armistead S, Lemire K, Orrell J, Teich J, Chomicz S and Ferrick DA., Am J Physiol Cell Physiol 292:C125-C136, 2007.

• LDH-A inhibition, a therapeutic strategy for treatment of hereditary leiomyomatosis and renal cell cancer.

  Xie H, Valera VA, Merino MJ, Amato AM, Signoretti S, Linehan WM, Sukhatme VP, Seth P., Mol Cancer Ther. 2009 Mar;8(3):626-35, (2009)

• Polo-like kinases mediate cell survival in mitochondrial dysfunction.

  Matsumoto T, Wang PY, Ma W, Sung HJ, Matoba S, Hwang PM., (2009) Proc Natl Acad Sci U S A., Aug 25;106(34):14542-6. (XF24 data is in the supplement to this paper).

Recent Cancer Metabolism Posters

• Metabolic Dependency on Fatty Acid Oxidation of Glioblastoma SF188 Cells

  Lisa S. Pike, Denise Chen, David A. Ferrick, and Min Wu; Seahorse Bioscience
  Keystone Conference Metabolism and Cancer Progression
  March 12-17, 2010
  Vancouver BC

• Cells addicted tp BCL-XL accumulate succinate via pyruvate carboxylase metabolism and glutaminolysis.

  Daciana Margineantu and David Hockenbery, Human Biology and Clinical Research Divisions, Fred Hutchinson Cancer Research Center
  AACR Metabolism & Cancer Conference
  September 13-16, 2009
  La Jolla, CA

• Bioenergetic differences in breast cancer cell lines

  Dilshan S. Harischandra and David Hockenbery, Iowa State University and Fred Hutchinson Cancer Research Center
  AACR Metabolism & Cancer Conference
  September 13-16, 2009
  La Jolla, CA

• 2-Deoxyglucose Induces a Metabolic Switch to Mitochondrial Oxidative Energy Metabolism Resulting in Sensitization to Apoptosis of Glioblastoma Cells

  2006 Gordon Research Conference on Cell Death
  September 10-15, 2006
  Big Sky Resort
  Big Sky, MT
  

• Real-time Metabolic Analysis of Glioblastoma Cells Treated with 2-Deoxyglucose Reveals a Metabolic Switch to Aerobic Energy Metabolism Mediated by HIF-1a

  AACR 2006 Annual Meeting
  April 1, 2006
  Washington, DC

• A Novel Assay for Profiling Metabolic Changes Mediated by HIF-1a in Cancer Cells

  Tumor Metabolism Summit
  September 19, 2005
  Genoa, Italy

• A Non-destructive, Time-resolved, Multi-analyte Technology for Sensing Metabolic Changes in Cancer Cells

  American Association for Cancer Research
  April 19, 2005
  Anaheim, CA