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September 25, 2007

Nanosensors help find how cancer establishes foothold in the body

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 body’s 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.

This news combines with other recent news about how some people are highly immune to cancer and how that stronger immunity could be transferred with a blood transfusion to other people. Cancer is the second most common cause of death in the United States after heart and coronary disease. If cancer were cured there would be about a 20% reduction in annual deaths.

Cancer uses a double pronged attack on T-cells which are the bodies defense against disease. By knowing how cancer and other diseases are defeating the immune system, then researchers can create ways to disrupt the attack on T-cells, kill the cancer cells, reverse the effects or create immunity to it.

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 don’t 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.

“It’s 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, which wipes T-cells out.”

“Our FRET technology with the novel tryptophan nanosensor has an added bonus,” said Thijs. “It can be used to identify new drugs that could reduce the ability of cancer cells to uptake tryptophan or their ability to degrade it. We believe that this technology could be a huge boost to cancer treatment.”

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