‘Finally,’ Brugge said, ‘we want to understand sufficiently the metabolism of cancer cells so that new types of drugs can be designed to target them.’Both strategies have worked. The cells with the gene for breast cancer discovered glucose transport, preventing the accumulation of ROS, and have found their level of ATP. Cells treated with antioxidants also survived, but by using fatty acids instead of glucose for energy.
This research was funded by the National Cancer Institute and National Institutes of Health.
Now, researchers at the Laboratory of Harvard Medical School professor of cell biology Joan Brugge have uncovered another mechanism that kills precancerous cells homeless. By studying two different types of human mammary epithelial cells, the researchers found that when separated from their natural environment, these cells lose the ability to harness energy from their environment. Finally, they are hungry.
‘Initially we thought that for cells to survive outside of their normal environment, they would simply need to suppress apoptosis,’ says Brugge, senior author on the paper that appears online Aug. 19 in Nature. ‘But our studies show that this activity is not sufficient to prevent cell loss homeless.’
Surprisingly, the metabolic function is restored if antioxidant activity is increased in cells, allowing cells to use energy pathways that do not rely on glucose.
The authors caution against extrapolating too far from their data, which were based on laboratory experiments in cultured cells. They also stress that the experiments were not designed to mimic the effect of antioxidants in the body. The researchers used two specific antioxidant compounds that are chemically distinct from those found in foods and supplements for the sole purpose of understanding how oxidants contributed to metabolic defects.
Atlantic coast of North America, which may engage in transcontinental migrations, such as shorebirds and gulls, ‘said Pearce.
Researchers had previously reported that when cells were provided with a carcinogenic gene that prevents them from committing suicide, even dead when cut off from their extracellular environment. This puzzled researchers, who have long thought that apoptosis is the only way the cells could die.
To understand what was wrong, researchers have adopted a simple approach have tried to solve the problem. Schafer cells designed to express high levels of homelessness of the HER2 gene, known to be hyperactive in many cancers of the breast. He also treated the cells with antioxidants in an attempt to relieve oxidative stress and help cells survive.
The researchers are now planning to test the effects of antioxidant genes, some of which are abnormally regulated in human tumors, and a wider range of antioxidants in animal models. They also intend to characterize the metabolic consequences of the gap matrix in more detail.
‘The idea that the absence of extracellular matrix can prevent the access of nutrients to the cells has not been shown conclusively before,’ says Schafer.
‘Loss of glucose transport, decreased ATP production, increased oxidative stress all these things seem to be closely related.’