28.02.2014 - 07:39
Research by Memorial Sloan Kettering, directed by the Catalan oncologist Joan Massagué offers news about the biologic mechanisms that individual cancerous cells use to metastasize in the brain. The study, published in the February 27th issue of Cell magazine, determines that the tumor cells that get to the brain and manage to form new tumors embrace the capillaries and give off specific proteins that can overtake the natural defenses of the brain against metastasis. Massagué indicates that the research could show the way toward preventing metastasis in various organs at once.
Metastasis, the process that allows some cancerous cells to expand beyond the original tumor and implant themselves in different tissue, is the most common cause of cancer deaths. Metastasized brain tumors are ten times more common than primary brain cancers.
Most tumor cells die before being able to implant themselves in the brain, which is better protected than most organs against the colonization of circulatory tumor cells. To implant itself in the brain, a cancer cell has to separate from its tumor of origin, enter into the blood stream, and cross dense blood receivers called brain blood barriers. Until now, little research had been done about how metastasize cerebral tumors develop, but previous experiments with mice that simulated metastasized breast cancer cells showed that only one out of a thousand cells that make it to the brain survive there.
“We didn’t know why so many of these cells were dying,” said Joan Massagué, director of the Sloan Kettering Institute and principal author of the study. “What kills them? And why do some of them survive in such a vulnerable state—sometimes hiding in the brain for years—and then all of a sudden expand into new tumors? What keeps these strange cells alive and where do they hide?”
In the study, they found that in models of mice with breast and lung cancer—two types of tumors that often extend to the brain—numerous cancel cells that get into the brain die from astrocytes. Astrocytes are the most common kind of brain cells and secrete a protein called Fas ligand.
When the cancer cells come into contact with this protein, they are forced to destroy themselves. The few that can avoid the astrocytes do so by producing a protein called Serpin that acts like a kind of antidote against the death signals sent by the astrocytes.
After producing triumphing metastasized cells in mice brains, the researchers realized that the cells that were able to survive were those that grew next to blood capillaries, with each cell stuck next to its recipient “like a panda bear embracing the trunk of a tree”, in Massagué’s words. They found that the tumor cells produce a protein that acts like velcro to adhere the cells to the external walls of the blood receiver.
“This adhesion is clearly essential,” said Dr. Massagué. “If a tumor cell disconnects from its recipient, it is eliminated by the nearby astrocytes. If not, it is nourished and protected, and at some point, can begin to divide and form a cover around its recipient.”
Under the microscope, the researches observed that some of these cancel cell covers around blood capillaries grew into small balls, which eventually formed tumors. “Once you’ve seen it, you can’t forget the image,” says Massagué.
Survival factors of the tumor cells discovered in this study could be treated with medicines some day in order to reduce the risk of metastasis in humans. Dr. Massagué is particularly interested in the ability of tumor cells to embrace their blood recipients, since he suspects that this behavior is essential for the survival of the metastasized cancer cells not only in the brain, but also in other parts of the body where cancer metastasis occurs.
“Most cancer patients suffer from the risk that their tumors will spread to different locations,” underscored Dr. Massagué. For example, breast cancer can spread to the bones, lungs, and liver, as well as the brain. “What we might be observing,” he added, “is the future path toward preventing metastasis in various organs at once” using medicine that can make the cancer cells disconnect from the blood recipients that they’re adhered to.”
