Protein Destroys Migrating Cancer Cells On Contact

In a study published online this week in the Proceedings of the National Academy of Sciences, a US team of biomedical engineers demonstrates a way to stop migrating cancer cells dead in their tracks as they travel through the bloodstream to set up new tumors.

Metastasis is where cancer cells from a first tumor detach and spread to other parts of the body. Surgery and radiation are usually quite effective for treating primary tumors, but once cancer cells start migrating the chances of successful treatment worsen considerably, partly because they are difficult to track down. The vast majority of deaths from cancer are due to metastasis. Now, a new study suggests it is possible not only to locate these migrating cancer cells, but to annihilate them before they have a chance to set up secondary tumors. Senior Researchers at Cornell University, Ithaca, New York, explain: "These circulating cancer cells are doomed. About 90% of cancer deaths are related to metastases, but now we've found a way to dispatch an army of killer white blood cells that cause apoptosis - the cancer cell's own death - obliterating them from the bloodstream. When surrounded by these guys, it becomes nearly impossible for the cancer cell to escape." For their study, the Cornell team used human blood samples and later, mice, to test the effect of two proteins: an adhesive called E-selectin, and another protein called TRAIL (Tumor Necrosis Factor Related Apoptosis-Inducing Ligand - a protein that triggers suicide in tumor cells). Cancer cells 'kill themselves' when in contact with TRAIL-coated white blood cells. Together the two proteins formed a sticky coating around leukocytes - white blood cells found everywhere in the bloodstream. They found that once cancer cells came into contact with the sticky white blood cells, they imploded.

One surprising factor was that the chaotic environment of a flowing medium, the bloodstream, actually improved the chances this would happen. When they tested the approach in a still medium, it was not as effective. And targeting the cancer cells directly with proteins, was not as effective either. It seems the best way was to turn the white blood cells into sticky carriers of the killer TRAIL protein. For instance, when they targeted the cancer cells in saline directly with the proteins, the success rate was 60%. But when they tried again with a model of flowing blood that has forces, mixing and other conditions similar to the human body, the kill rate shot up to 100%. The authors write: "The mechanism is surprising and unexpected in that this repurposing of white blood cells in flowing blood is more effective than directly targeting the cancer cells with liposomes or soluble protein." Funds from the National Cancer Institute of the National Institutes of Health helped finance the study. Meanwhile in another study published recently in Cell, another US team described how they stopped the first step of breast cancer spread in mice. They discovered that by knocking out a protein in a class of cells that leads the migration, they could render them incapable of carrying out the first crucial step of metastasis.