SLEEPERS: A new study reveals that blood vessel-forming stem cells from bone marrow (green) trigger the expansion of breast cancer cells (blue) that have budded off from the primary tumor.
Researchers say they have identified a switch that makes dormant breast cancer cells that have traveled to the lungs swell to lethal proportions—completing the dreaded process of metastasis or cancer spread. A team from Cold Spring Harbor Laboratory in Long Island, N.Y., reports that it staved off full-blown metastasis in mice by preventing mini-tumors in the lungs from recruiting stem cells called endothelial progenitors, which assemble into blood vessels to nourish the malignancy.
Researchers do not know if the same thing would work for other types of cancer or cancer cells lodged in other body organs. Still, they hope to discover drugs that could put the brakes on at least some metastases by short-circuiting the ability of endothelial progenitors to respond to chemical cues sent out by tumors.
As tumors grow and develop, they shed micro-metastases, clusters of a few cells that take up residence in far-flung organs such as the brain, liver and bone. Without new vessels to bring them fresh nutrient-rich blood, however, they may lay dormant for years before suddenly sprouting into macro-metastases large enough to damage organs and cause death.
"They're sleeping and suddenly they wake up, and that's very dangerous," says Cold Spring cancer biologist Vivek Mittal. Metastatic cancer is rarely curable.
To explain the so-called angiogenic switch, or sudden growth of new blood vessels, some have pointed to endothelial progenitors, which live in bone marrow but are found in more than half of all solid tumor types, says hematology oncologist Shahin Rafii of Weill Cornell Medical College in New York City. Their significance wasn't clear, though, given that they only account for 12 to 15 percent of a tumor's blood vessels.
To clarify their role, the Cold Spring group allowed breast tumors implanted in mice to form micro-metastases in the lungs. The team then introduced short RNA molecules that deactivate a gene called Id1, which promotes angiogenesis and is active in endothelial progenitors.
Treated mice formed fewer tumors and showed less angiogenesis, and half survived to day 40, whereas all untreated mice died within 30 days, the group reports in Science. The treated mice also showed a 96 percent reduction in the flow of endothelial progenitors from bone marrow to lung.
"It's very novel," says Rafii, who was not involved in the study. "You shut off 12 percent of cells, and 50 percent of the mice survive much longer."
He says that the mechanism is unlikely to work in all tumor types or metastases, but that it is definitely worth exploring its potential ability to turn some fatal cancers into chronic diseases. "At least in mouse systems it works, so it has to be tested in humans eventually."
