Scientific study directed by Dr. Joan Massagué uncovers the mechanisms of brain metastasis

Barcelona (ACN).- A scientific research conducted at the Memorial Sloan-
Kettering Centre in New-York, and directed by Catalan Oncologist Joan Massagué has shed light on the biological mechanisms used by cancer cells to metastasise in the brain. The study, published in the 27th magazine, reveals that cancer cells which manage to form new tumours in the brain, do so by attaching themselves to capillaries and secreting special proteins to overpower the brain’s defence mechanisms. According to Dr. Massagué - recently appointed Scientific Director of the Sloan Kettering Institute for leading the way in research on metastasis and cell-growth - the study could be instrumental in preventing and treating Multiple-Organ-Metastasis.

Metastasis, the process through which tumerous cells spread from one organ or tissue to other parts of the body, is the most common cause of death for patients diagnosed with cancer. Metastasised brain tumours are ten times more common than primary brain cancers.

Only 1 out of 1000 cells reaching the brain can survive there

The majority of tumerous cells die before being able to implant themselves in the brain, which is less vulnerable than most other organs to cancer cell migration. In order to spread to the brain, cancer cells have to break away from their initial tumour, enter the blood stream, and cross the highly selective brain-blood barrier, composed of high- density cells and separating the blood circulation system from the brain extracellular fluid. Until now, only little research had been done on how metastasised brain tumours develop, but past experiments on cancer cell migration, conducted on mice, have indicated that of only one out of a thousand cells reaching the brain can survive there.

How can this minority of cancer cells that successfully spreads to the brain survive?

“We didn't know why so many of these cells were dying” explained the main author of the study, Doctor Joan Massagué, who was recently appointed Scientific Director of the Sloan Kettering Institute, the leading cancer research centre in the world. “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 expanding into new tumours? What keeps such strange cells alive and where do they hide?” wondered the Catalan scientist, who is also the Vice-Director of Barcelona’s Institute for Research in Biomedicine.

Secreting a protein to fight against the brain’s cell killing astrocytes

During their research, the scientists discovered that in the case of mice suffering from breast and lung cancer—two types of tumours that often spread to the brain—many cancer cells that reached the brain were killed by astrocytes. Astrocytes are the most common kind of brain cells and secrete a protein called ‘Fas ligand’, belonging to the ‘Tumor necrosis factors’ family as it can cause cell death.

Indeed, when the cancer cells come into contact with this protein, they are forced to self-destruct. The few of them that can avoid the astrocytes do so by producing a protein called serpin, which acts like an antidote against the death signals sent by the astrocytes.

Sticking to capillaries to be protected and develop into new tumours

After susses fully reproducing metastasised cells to overcome the defence mechanisms of mice, the searchers found out that the cells that were able to survive in the mice’s brain were those that grew next to blood capillaries, with each cell attached to its own blood vessel “like a panda bear embracing the trunk of a tree”, in Dr. Massagué's words. The scientists discovered that the cancer cells could produce a protein acting like a Velcro to stick to the walls of capillaries.

“This adhesion is clearly essential” said the Catalan Scientist. “If a tumour 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 sheath around the blood vessel”.

Under the microscope, the searchers observed that some of the cancer cell that covered blood capillaries grew into small balls, which eventually formed tumours. “Once you've seen it, you can't forget the image” stated the Scientific Director of the Sloan Kettering Institute.

Reducing the risks of metastasis for patients

The tumour cells’ capacity for survival, which was uncovered with this study, could be medically treated in the future in order to reduce the patients’ risks of metastasis. Dr. Massagué is particularly interested in the tumour cells’ ability to attach themselves to blood vessels. Indeed, he suspects that this behaviour is essential for the survival of the metastasised cancer cells not only in the brain, but also in other parts of the body where metastasis is likely to occur.

“Most cancer patients suffer from the risk that their tumour will spread to multiple other parts [of the body]” explained the Catalan Scientist. Breast cancer, for instance, can spread to the bones, lungs, and liver, as well as to the brain. “What we might be looking at”, he added, “is the future path toward preventing metastasis in multiple organs at once” using medicine that can make the cancer cells detach themselves from the blood vessels that they have been sticking to.