1. Joan Massagué i Manuel Valiente: Descoberts mecanismes desencadenants de la metàstasi del càncer

2. Memorial Sloan Kettering: “Study reveals mechanism cancer cells use to establish metastatic brain tumors”

1. Joan Massagué i Manuel Valiente: Descoberts mecanismes desencadenants de la metàstasi del càncer

La investigació podria servir de base per al desenvolupament de fàrmacs efectius contra l’expansió de tumors

Els científics Joan Massagué i Manuel Valiente han descobert els mecanismes que causen l’expansió desenfrenada del càncer entre els òrgans, la principal causa dels diagnòstics més pessimistes per als malalts. La determinació del mecanisme imprescindible per a les metàstasi és crucial per trobar els mètodes per desactivar el desenvolupament de la proliferació de les cèl·lules i reduir per fi de manera significativa les elevades taxes de mortalitat del càncer. Els dos científics, des del seu lloc de treball al Centre Memorial Sloan Kettering de Nova York (EUA) ja ha començat a discriminar i avaluar l’acció dels anticossos necessaris per frenar el càncer en ratolins. Com en qualsevol investigació, és una línia de treball esperançadora però que té al davant encara un ardu camí de proves i experiments.

La determinació dels mecanismes desencadenants de les metàstasis és fonamental per atacar l’elevada mortalitat del càncer. Tumors inicialment de caràcter lleu es poden convertir en mortals de necessitat si es produeix una expansió descontrolada de les cèl·lules cancerígenes a altres òrgans vitals.

Segons la nota de premsa difosa pel Memorial Sloan Kettering, els estudis s’han centrat en l’anàlisi de processos metastàsics que afecten el cervell i els enzims generats per defensar-se de l’agressió. La peça clau del trencaclosques és la denominada plasmina, un enzim que segons els investigadors del Memorian Sloan Kettering serveix per combatre l’expansió de les cèl·lules cancerígenes a l’evitar el transport d’aquestes a través de l’aparell circulatori. El que han fet Massagué i Valiente és analitzar els mecanismes que fan que algunes cèl·lules aconsegueixin evitar l’acció d’aquest enzim protector. El repte ara és trobar el fàrmac o catalitzador capaç d’inhibir les defenses d’aquestes cèl·lules cancerígenes resistents. Els dos investigadors consideren que mitjançant l’experimentació amb ratolins seran capaços d’aconseguir aquest objectiu.

El Periódico, 28/02/2014

2. Nota del Memorial Sloan Kettering: “Study reveals mechanism cancer cells use to establish metastatic brain tumors”

New research from Memorial Sloan Kettering provides fresh insight into the biologic mechanisms that individual cancer cells use to metastasize to the brain. Published in the February 27 issue of Cell, the study found that tumor cells that reach the brain — and successfully grow into new tumors — hug capillaries and express specific proteins that overcome the brain’s natural defense against metastatic invasion.

Metastasis, the process that allows some cancer cells to break off from their tumor of origin and take root in a different tissue, is the most common reason people die from cancer. Metastatic brain tumors are ten times more common than primary brain cancers.

Yet most tumor cells die before they can take root in the brain, which is better protected than most organs against colonization by circulating tumor cells. To seed in the brain, a cancer cell must dislodge from its tumor of origin, enter the bloodstream, and cross densely packed blood vessels called the blood-brain barrier. Until now, little research has been done into how metastatic brain tumors develop, but previous mouse experiments that imaged metastatic breast cancer cells over time have shown that of those cancer cells that do make it to the brain, fewer than one in 1,000 survive.

“We didn’t know why so many of these cells die,” says Joan Massagué, PhD, Director of the Sloan Kettering Institute and senior author of the study. “What kills them? And how do occasional cells survive in this vulnerable state — sometimes hiding out in the brain for years — to eventually spawn new tumors? What keeps these rare cells alive and where do they hide?”

In the Cell study, Dr. Massagué, with Fellow Manuel Valiente, PhD, and other team members, found that in mouse models of breast and lung cancer — two tumor types that often spread to the brain — many cancer cells that enter the brain are killed by astrocytes. These killer cells, the most common type of brain cell, secrete a protein called Fas ligand.

When cancer cells encounter this protein, they are triggered to self-destruct. The exceptional cancer cells that escape the astrocytes do so by producing a protein called Serpin, which acts as a sort of antidote to the death signals fired at them by nearby astrocytes.

After imaging defiant metastatic cells in the brains of mice, researchers noticed that the cells that were able to survive grew on top of blood capillaries, each cell sticking closely to its vessel “like a panda bear hugging a tree trunk,” Dr. Massagué says. They found that the tumor cells produce a protein that acts like Velcro to attach the cells to the outer wall of a blood vessel.

“This hugging is clearly essential,” Dr. Massagué explains. “If a tumor cell detaches from its vessel, it gets killed by nearby astrocytes. By staying on, it gets nourished and protected, and may eventually start dividing to form a sheath around the vessel.”

Under the microscope, the researchers watched these sheaths of cancer cells around the blood capillaries grow into tiny balls, which eventually became tumors. “Once you’ve seen it, you can never forget this image,” Dr. Massagué says.

The tumor-cell survival factors uncovered by this study might one day be targeted with drugs to further diminish people’s risk of metastasis. Dr. Massagué is particularly interested in the ability of tumor cells to hug blood vessels, as he suspects this behavior may be essential for the survival of metastatic cancer cells not only in the brain but also in other parts of the body where metastatic tumor growth can occur.

“Most cancer patients are actually at risk of having their tumor spread to multiple sites,” Dr. Massagué notes. For example, breast cancers can metastasize to the bones, lungs, and liver, as well as to the brain. “What we may be looking at,” he adds, “is a future way to prevent metastasis to many organs simultaneously” using drugs that make tumor cells let go of the blood vessels they cling to.

Memorial Sloan Kettering Cancer Center

We are the world’s oldest and largest private cancer center, home to more than 12,000 physicians, scientists, nurses, and staff united by a relentless dedication to conquering cancer. As an independent institution, we combine 130 years of research and clinical leadership with the freedom to provide highly individualized, exceptional care to each patient. And our always-evolving educational programs continue to train new leaders in the field, here and around the world. For more information, go to http://www.mskcc.org.

Memorial Sloan Kettering Cancer Center, New York, February 27, 2014

  Cancer, Medecina