“Don’t eat me” sign helps bladder tumors escape
Researchers said on Monday they had found primitive bladder cancer cells that cloak themselves with a “don’t eat me” signal that scares off immune system cells, allowing them to mature into tumors later on.
But they found a way to unmask this disguise and said their findings may lead to new approaches for treating cancers of several different types.
The immediate hope is to find a way of telling apart patients who have dangerous bladder cancer from those who have more benign forms. Bladder cancer is mostly slow-growing and easily treated, but 15 percent of cases become invasive and deadly.
Dr Irving Weissman of Stanford University in California and colleagues found that the so-called cancer stem cells disguise themselves using a protein called CD-47. Immune system cells called macrophages usually eat cancer cells but CD-47 is a signal that turns them off.
“This is first time we’ve found this ‘don’t eat me signal’ in a stem cell of a solid cancer,” Weissman said in a statement. “We’re now moving as fast as we can to look at other tumors to see if this is a universal strategy of all or most cancer stem cells.”
The same team earlier found that some types of leukemia cells also use CD-47 as a disguise. Samples from bladder tumors showed that most were rich in CD-47.
Weissman’s team found that CD-47 was expressed more, meaning it was more active, among cancer cells from patients who went on to develop the dangerous kind of bladder tumor. They think they can use this unique pattern to help diagnose patients better, allowing those with aggressive cancers to get more immediate treatment.
They also used a monoclonal antibody—an engineered immune system particle that recognizes a single protein—to block the CD-47 disguise. Tumor cells soaked in a lab dish with the antibody were later destroyed by macrophages, Weissman’s team reported in the Proceedings of the National Academy of Sciences.
Monoclonal antibodies are already used in several cancer drugs, including Roche AG’s Rituxan or MabThera, Herceptin and Avastin.
SOURCE: Proceedings of the National Academy of Sciences, advance online publication, August 3, 2009.
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