The findings could change the way all cancers are understood and ultimately treated, claims a team of 16 scientists from two New York research centers, Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University.
"We believe we have identified the factors that encourage the growth of malignant tumors, as well as possible ways to turn off that growth," says study co-author Robert Benezra, a Sloan Kettering scientist who spearheaded the research with Dr. David Leyden.The factors pinpointed by the study are the ordinary bone marrow cells that are called into action at the very earliest stages of cancer development and that appear to play a critical role in a process called angiogenesis -- the formation of blood vessels to feed tumors.
"Before you can build the building, you have to lay down the roads to bring in the supplies, and angiogenesis is that road-building process, helping bring nutrients to the tumor," says study co-author Dr. Shahin Rafii, a Cornell scientist whose initial research helped launch the study.
Although the concept of angiogenesis is not new, the latest study defines how and why it occurs, as well as what can keep it from occurring to prevent tumor growth.
Not all doctors, however, are impressed with the finding.
"There are a lot of factors that come into play in angiogenesis," says Dr. Ruth Oratz, a breast and ovarian cancer specialist and associate professor of medicine at New York University Medical Center. "There are many cells and many cascades involved, and some of those cells may derive from the bone marrow, [but] I don't see what's so exciting about that."
The researchers say the exciting part of the finding is that the switch that turns on angiogenesis appears to sit in a cache of dormant bone marrow cells in all healthy adults.
"These are cells that play a role in the development of our body in the fetal stage, but appear to have no function in the adult body until malignant cells are present," Benezra says.
Reawakened by the presence of malignant cells, a protein found in the marrow stimulates the release of two different types of bone marrow cells into the blood stream, where they speed to the tumor site, the study says. Once there, they help initiate angiogenesis.
"In at least two types of cancer, lymphoma and lung cancer, we have shown that it is impossible for tumors to grow without these bone marrow cells," Rafii says. Other cancers, including breast cancer, also are thought to be affected by these same cells, he says.
But what specifically "wakes up" these dormant cells and gets them moving?
Rafii says it's a biochemical signal emitted by the developing malignant cells, a hormone-like substance known as the human growth factor VEGF.
Like a moth to a flame, he says the bone marrow cells are drawn to the source of VEGF -- the developing tumor. Once there, the process of angiogenesis begins.
The scientists say they have proved their theory with a strain of mice bred without the key bone marrow protein. Malignant cells were put into the mice, but without that protein, bone marrow cells did not receive the wake-up call, the researchers report. Angiogenesis could not take place, and tumors would not grow, they say.
But when the protein was transplanted into the mutant mice, the switch was thrown. Bone marrow cells were activated, and the tumor-growing process flipped into high gear, the study says. That's when the researchers say they fully realized what they had discovered.
"These same mice that could not grow tumors before were suddenly developing tumors," Benezra says. Details appear in the Nov. 1 issue of Nature Medicine.
Oratz says the information has no immediate use. "There's lots and lots of experiments going on. This is an interesting piece of data, but it has no immediate clinical relevance."
Others see it differently.
For instance, Benezra says non-toxic treatments might be created that could turn off the protein that stimulates the release of the bone marrow cells in the first place, keeping tumors from ever developing. So far, at least one company, Angiogenics -- which funded some of the current research -- has begun developing such a treatment.
Rafii says another approach could involve the development of what he calls a kind of biological cruise missile.
"Since we now know that the tumor is calling these bone marrow cells to the site, one possible treatment is to extract these cells, load them with drugs designed to kill the tumor, plant them back in the body and then watch them head towards the tumor and destroy it," Rafii says.
And Benezra says Sloan Kettering is working on a blood test to measure circulating levels of VEGF.
"This will act as a marker for cancer, alerting us to the presence of disease before a tumor can even be seen," he says. That test is expected to be available in the foreseeable future, he says.
What To Do: For a primer on various aspects of cancer, including diagnosis and treatment, go to CancerNet, sponsored by the National Cancer Institute. To learn more about angiogenesis, visit the Dana Farber Cancer Center.