“This is the first time we’ve found this ‘don’t eat me’ signal in a stem cell of a solid cancer,” said Irving Weissman, the Virginia & D.K. Ludwig Professor for Clinical Investigation in Cancer Research at the medical school. “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.” If so, scientists may be able to devise a way to neutralize the “don’t eat me” signal for the stem cells of many cancers. And if they’re able to identify and follow the cells, they may be able to find a good way to measure the decline of a tumor, too.
The notion of cancer stem cells was only just emerging back in 2002. Since then, research has shown that these stem cells, like evil queen ants, busily replenish their “nest” of cancer cells. It’s believed that, even though chemotherapy and radiation can kill tumor cells, unless the stem cells are destroyed, the cancer will grow back.
“The whole concept of cancer stem cells is that they are often resistant to current therapies,” said Keith Syson Chan, who is the first author of the study, published in the Proceedings of the National Academy of Sciences, “and, at least in the case of bladder cancer, they drive the progression of the disease.”
Weissman is the senior author of the paper. Not long ago, his laboratory published two studies in the journal Cell showing that human leukemia stem cells use a protective molecular device on their surface to elude the body’s “garbage disposal” cells, known as macrophages. These cells swallow up and digest sick or cancerous cells. Their protective molecular device turned out to be identical to the one used by bladder cancer stem cells.
“Leukemia is totally different from the kind of epithelial cancer we see in the bladder,” said Chan, “so it was very exciting to see that these two kinds of cancer stem cells use a similar mechanism to escape the macrophages. It’s also very interesting to find that macrophages seem to be playing such a major role in cancer progression.”
Of the two chief kinds of bladder cancer, one aggressively invades the muscle around the bladder and spreads to other organs. The other stays within the bladder lining. The aggressive version, which comprises about 30 percent of bladder cancers, is generally incurable. Some 15 percent of the non-invasive kind progresses to invasiveness, but there is currently no way of predicting this progression.