Despite the multiple weapons that medicine has developed and perfected to fight cancer –surgery, radiotherapy, chemotherapy… – that arsenal is of little use to us if a single malignant cell manages to escape alive and, like a fierce soldier, spreads by blood or lymph to other tissues. When this process, the much dreaded metastasis, culminates in the colonization of one or more organs and tissues by new armies, it is possible that neither the surgeon, nor the medications, nor the body’s own defensive system have options to deal with it successfully. .
To further complicate the situation, metastatic cancer can lie dormant for years or decades after it has spread. And one fine day, without warning, it begins to grow aggressively, with a predilection for four organs: the bones, the lungs, the liver and the brain. Given their modus operandi, it is not surprising that 90% of deaths are attributed to malignant tumors.
The worst thing is that the leaked cells are also the smartest or, as Joan Massagué defines them, the “most evolved”. According to this Catalan metastasis expert, “they can only infiltrate an organ if they have the necessary skills to pass through its capillaries. After this selection, those that are also equipped with functions to survive in the new environment will be viable. And finally, newly arrived tumor cells will metastasize only to the extent that they are capable of evolving and adapting ”. In other words, Darwin’s theory would also apply to this evil phenomenon .
If we were to make a robot portrait of a metastatic cell, the most distinctive feature would be its ability to pass through walls: those of blood vessels. Scientists at the University of Zurich have shown that, at least in part, this superpower is conferred by a protein called CCL2. This tricks and manipulates the receptors or molecular gatekeepers of the endothelium – tissue that lines the interior of arteries, veins and capillaries – to open their doors to the blood. Elevated levels of CCL2 chemokine are characteristic, above all, of metastases arising from cancers of the breast, prostate, and intestine .
In addition, scientists from the University of Arizona have concluded that invading cells have structures called invadopodia, a kind of protuberance or feet that allow them to pass from one organ to another, opening gaps in the tissues. It is as if they were setting up a tent: after projecting a portion of their rigid internal scaffolding towards the cell membrane, they extend a long and thin protrusion towards the extracellular matrix r – the medium in which the cells are immersed – that would help them to move .
Another of their characteristic features is how little it costs them to make friends. In fact, scientists have discovered that they have more cronies infiltrated into our bodies than we imagined; among them, platelets. Biologists from the Massachusetts Institute of Technology (MIT) found that this component of the blood, responsible for wound healing, is also secretly responsible for helping malignant cells to grow, to cross the partitions of the vessels, to navigate the torrent blood and to settle in new tissues. In other words, “they teach them what they do best,” concluded Richard Hynes and his colleagues in the journal Cancer Cell .
But they are not the only traitors. A recent Yale University review published in the journal Nature Reviews Cancer reveals that the starting point of metastases is due to the genesis of a hybrid between the messenger of evil and a white blood cell , which as part of the immune system has free way to move throughout the body. The hypothesis was originally raised nearly a century ago, and now there are more than a dozen studies that seem to back it up.
On the other hand, stellate cells, which normally help us respond to injury or disease of the pancreas, can act as dual agents . A team of experts from the University of Oxford showed that they not only stimulate the growth and spread of a tumor in that organ, but also travel in tandem with the cells that cause metastasis and protect them against radiation. Thus, they help them settle into their new home “more comfortably and quickly,” as the authors of the research, published in the American Journal of Pathology, explain. If a mechanism were developed to block the necessary collaborators, it would improve the success of the treatment of pancreatic cancer, one of the most damaging that exists: only 20% of diagnosed patients live a year or more.
Because you have to pay close attention to the apparently innocuous neighborhood of tumors: they also become stronger and more aggressive when there are cells that are too old – senescent, unable to divide – and that practice autophagy or autocannibalism, as demonstrated ago little Michael P. Lisanti, an expert in regenerative medicine at Thomas Jefferson University, in the USA.
Apart from internal biological factors, emotional circumstances accelerate harmful migration to other organs , according to a study in the journal PLOS Biology . Specifically, stress and depression make breast cancer cells race to colonize bone, in addition to reducing patient survival. Researchers attribute this to the fact that the activation of the sympathetic nervous system, responsible for the human fight or flight response to dangerous situations, favors metastasis. Scientists at the University of Western Ontario, in Canada, have made even more concrete and have shown that chronic stress increases the release of two neurotransmitters, norepinephrine and neuropeptide Y, which give the disease the definitive push to leave the primary tumor and spread.
Fortunately, we know more and more about the adversary we face. And not only what is necessary to defend ourselves from him, but even to prevent him from attacking. After all, as the Chinese military man and philosopher Sun Tzu said, “the supreme art of war is to subdue the enemy without fighting.”
In this sense, a new contribution from the Massachusetts Institute of Technology (MIT) reveals that certain cell adhesion molecules are critical in the process. ” The more metastatic a cancer is, the more ability it has to stick to healthy tissue structures and grow on them , multiplying its aggressiveness,” explains Sangeeta Bhatia, co-author of the work and researcher at the David H. Koch Institute for the Study. Comprehensive Cancer, in Massachusetts.
A promising ally could be pomegranate juice thanks to its content of phenylpropanoids, hydroxybenzoic acid, flavones and fatty acids, since, according to researchers at the University of California, these substances prevent the prostate tumor from expanding throughout the body. In addition, as recently published in the journal Cell , researchers at the Peter MacCallum Center in Melbourne, Australia, have discovered the mechanism by which certain non-steroidal anti-inflammatory drugs, such as the classic aspirin, can also reduce the spread.
To this is added that, as announced by scientists from the California Pacific Medical Center, cannabidiol or CBD – a compound in marijuana – is capable of deactivating the ID-1 gene, which triggers metastasis . For their part, specialists from the University of California at Santa Bárbara have shown that cruciferous vegetables, such as cabbage, broccoli and cauliflower, hinder the fatal spread – especially of breast tumors – thanks to their isothiocyanates, rich in sulfur . And the proanthocyanidins in grape seed not only prevent it, but also push globetrotting cells to commit suicide, a phenomenon known as apoptosis, or programmed cell death. This has been corroborated by a study from the University of Alabama.
But the danger can be further reduced if we initiate the siege even before the future invader gathers strength and escapes. Because, first, the tumor needs to create a network of blood vessels to feed itself . American and Norwegian scientists have discovered that this process, called angiogenesis, can be stopped by injecting prosaposin, a natural protein found in body fluids such as plasma and human milk. ” Even if we do not prevent patients from contracting cancer, we would keep them free of metastasis, ” commented Randolph S. Watnick, a researcher at Children’s Hospital Boston and a co-author of the work, following the finding.
Science may have a long way to go before beating cancer. Meanwhile, it is convenient to follow the premise of George Patton, the mythical North American commander of World War II, and bet that “a good plan today is always better than a perfect one tomorrow.”
