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Scientists discover how cancer may take hold
Date:9/24/2007

Stanford, CA-- A team, led by researchers at the Carnegie Institution,* has found a key biochemical cycle that suppresses the immune response, thereby allowing cancer cells to multiply unabated. The research shows how the biomolecules responsible for healthy T-cells, the bodys first defenders against hostile invaders, are quashed, permitting the invading cancer to spread. The same cycle could also be involved in autoimmune diseases such as multiple sclerosis. The work is published in the September 25, 2007, issue of PLoS Biology.

The scientists used special molecular nanosensors for the work. We used a technique called fluorescence resonance energy transfer, or FRET, to monitor the levels of, tryptophan, one of the essential amino acids human cells need for viability, explained lead author Thijs Kaper. Humans get tryptophan from foods such as grains, legumes, fruits, and meat. Tryptophan is essential for normal growth and development in children and nitrogen balance in adults. T-cells also depend on it for their immune response after invading cells have been recognized. If they dont get enough tryptophan, the T-cells die and the invaders remain undetected.

The scientists looked at the chemical transformations that tryptophan undergoes as it is processed in live human cancer cells. When tryptophan is broken down in the cancer cells, an enzyme (dubbed IDO) forms molecules called kynurenines. This reduces the concentration of tryptophan in the local tissues and starves T-cells for tryptophan. A key finding of the research was that a transporter protein (LAT1), present in certain types of cancer cells, exchanges tryptophan from the outside of the cell with kynurenine inside the cell, resulting in an excess of kynurenine in the body fluids, which is toxic to T-cells.

Its double trouble for T-cells, remarked Wolf Frommer. Not only do they starve from lack of tryptophan in their surroundings, but it is replaced by the toxic kynurenines, w
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Contact: Wolf Frommer
wfrommer@stanford.edu
650-325-1521 x208
Carnegie Institution
Source:Eurekalert

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