Sensor Detects Lactate Levels in Individual Cancer Cells

A high rate of lactate production indicates that cancer is present, via diagnostics such as positron emission tomography (PET) scans, and may offer an opportunity for novel cancer therapies.

The scientists used a bacterial transcription factor—a protein that binds to specific DNA sequences to control the flow of genetic information from DNA to mRNA—as a means to produce and insert the lactate sensor. They turned on the sensor in three cell types: normal brain cells, tumor brain cells, and human embryonic cells. The sensor was able to quantify very low concentrations of lactate, providing good sensitivity and range of detection. Sugars are broken up by cancer cells and produce the metabolic acid lactate at a much greater rate than normal cells. The tumor cells produced lactate three to five times faster than the nontumor cells.

“The high rate of lactate production in the cancer cell is the hallmark of cancer metabolism,” remarked Prof. Frommer. “This result paves the way for understanding the nuances of cancer metabolism in different types of cancer and for developing new techniques for combating this scourge.”

Chilean researchers from the Centro de Estudios Científicos (CECs; Valdivia, Chile) with the collaboration of Carnegie’s Institute of Washington (Washington DC, USA) Prof. Wolf Frommer devised the molecular sensor that detects levels of lactate in individual cells. Prior to this advance, no other measurement method could noninvasively detect lactate in real time at the single-cell level. The work, published in the February 26, 2013, edition of the open access journal PLOS ONE, is a boon to understanding how different types of cells go awry when cancer hits.

The biosensors also might be able to solve an old controversy. While some studies have suggested the glucose provides fuel for the brain, recent research has provided evidence that lactate feeds energy metabolism in neurons. Oxidation of lactate can be used to produce large amounts of adenosine tri-phosphate (ATP), the coenzyme that carries energy in cells. The Barros and Frommer teams are excited about the possibility of solving this enigma with the use of their new sensors, together with previously developed glucose sensors.

“Over the last decade, the [Wolf] Frommer lab at Carnegie’s Institution of has pioneered the use of Förster resonance energy transfer, or FRET, sensors to measure the concentration and flow of sugars in individual cells with a simple fluorescent color change. This has started to revolutionize the field of cell metabolism,” explained CECs researcher Alejandro San Martin, lead author of the article. “Using the same underlying physical principle and inspired by the sugar sensors, we have now invented a new type of sensor based on a transcriptional factor. A molecule that normally helps bacteria to adapt to its environment has now been tricked into measuring lactate for us.”

Related Links:
Centro de Estudios Científicos
Carnegie’s Institute of Washington