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TELLTALE MOLECULES displayed on the surfaces of cancer cells are helping scientists unlock the puzzle of metastasis, the most dangerous part of the cancer process.
The cell-surface signals - acting rather like dog tags showing a cell's identity - play crucial roles at almost every step of metastasis, which occurs when a tumor sends deadly "seeds" off to colonize other parts of the body.
A deep understanding of metastasis is important, said Dr. Bruce Zetter, at Children's Hospital in Boston, because it is metastasis, rather than the original tumors, which usually kills patients. And, he said, metastasis often begins before a patient ever sees a doctor.
"Half of all the people who have a primary tumor" and show up at a doctor's office seeking help "have metastases already in place," Zetter said. Metastasis is so insidious, in fact, that even patients showing no signs of cancer having spread end up, later, with tumors growing elsewhere.
"If you look at the five-year survival of patients who have no evidence of metastasis" when first diagnosed, Zetter said, "only half of them are alive." Those who died "were in a micrometastasis stage, a sort of metastatic dormancy. It's something nobody understands - how they {the spreading cells} can remain dormant for years."
Fortunately, because of extraordinary new biological techniques, scientists are beginning to see how cells break loose from a growing tumor and enter the circulation, select a suitable place to land, then slip out of the bloodstream to start new tumors. At each step, the chemical signals found on cell surfaces appear to play critical roles.
According to biologist Patricia Steeg, at the National Cancer Institute, "we are beginning to understand how tumor cells metastasize. Tumor cells do not just float from the primary tumor to other sites in the body; metastasis requires many changes in the cells' behavior."
Zetter said it's already clear that metastasis is not an efficient process. Even though a tumor only half an inch in diameter can shed 3 million cells per day into a patient's bloodstream, very few actually survive long enough to form tumors.
This suggests that the body's defense mechanisms keep mopping up most of the spreading cells before they can settle down and begin doing damage.
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