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Tumor life support. Bone marrow cells, in blue, have migrated to the tumor site (top); a special staining technique determines what kind of bone marrow cells they are (bottom).

Bone Marrow Feeds Hungry Tumors

Like the rest of the body, tumors need blood to survive, and a hot area of research involves finding ways to block that nourishment. Now, cancer researchers have discovered a new angle to this approach: By stopping the tumors from recruiting raw materials to build their network of blood vessels, a process called angiogenesis, they can prevent tumor growth.

Researchers used to think that tumors recruited new blood vessel cells from existing vessels nearby. Then, in 1999, a team discovered that when a set of genes called Id1-4 is disabled in mice, the animals cannot grow tumor blood vessels. Normally, the Id genes are active in embryonic development of blood vessels, and then turned off permanently after birth.

Cancer biologists David Lyden, Shahin Rafii, and Robert Benezra and a joint team from Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, and ImClone Systems Inc., all in New York City, wanted to find out if Id genes allow tumors to recruit building blocks from the bone marrow, which helps build blood vessels. Using mice that lacked Id genes and can't build new tumor blood vessels, Lyden's team replaced the mice's bone marrow with normal, Id-containing bone marrow. Then they implanted tumors under the animal's skin. Within hours, bone marrow cells migrated to the tumor.

Though previous estimates suggested that bone marrow cells made up 5% to 10% of new blood vessels, Lyden says, the new data suggest "the bone marrow is really responsible for the whole tumor blood vessel network." The researchers also developed antibodies to a receptor on the surface of the bone marrow cells that receives the come-hither signal from the tumors. These antibodies prevented blocked signals to the marrow and halted tumor blood vessel growth.

"Seminal" is how tumor angiogenesis researcher Judah Folkman of Harvard Medical School in Boston describes the work. "The concept that there is a steady traffic of precursor endothelial cells from bone marrow into the tumor bed is a very novel, important finding," he says. The results, he says, could open the door for a new class of antiangiogenic drugs that may help combat tumor growth.

Related sites

Abstract of Lyden et al. Nature Medicine paper
Rafii lab home page
Benezra lab home page
Lyden et al.'s 1999 Nature paper first linking Id proteins to tumor angiogenesis