Like a flock of birds or a school of fish, so cancer cells migrate moving in unison, as a single entity. And, suddenly, they’re acting like a fluid. It is (also) thus, by exploiting this biological and physical characteristic, that breast cancer acquires the ability to spread throughout the body. It was discovered by a group of Italian researchers with a basic physiology study that may seem very distant from what doctors and patients need to cure the disease, but which instead today reveals a possible weak point. He tells it to Salute Seno George Scythianhead of the ‘Tumor Cell Research Mechanisms’ laboratory of the Ifom (Molecular Oncology Foundation Institute), Professor of General Pathology at the State University of Milan and at the helm of this research, supported by the Airc Foundation.
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Professor Scythian, what exactly have you discovered?
“Already four years ago, with a first study published in Nature Materials, we observed that breast cancer cells ‘migrate’ in a collective and coordinated manner within the body, maintaining a strong interaction. Their migration strategies are very reminiscent those of groups of fish and birds, so much so that our analysis algorithms – developed with Fabio Giavazzi, a physicist at the University of Milan – derive precisely from studies on the movements of these animals.In this process, the cells undergo a sort of transition of state: as if they collectively became from solid to liquid. We can imagine them as a piece of ice that melts and expands. We started from here to understand the advantages, but also the disadvantages, of this transition for the tumor, and we are trying to understand what are the chemical, biological and physical laws that govern its migrations”.
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The benefits are clear, but you’ve also highlighted an Achilles heel, correct?
“Yes. In the new study, also published in Nature Materials and always carried out in close collaboration with Fabio Giavazzi, we observed that during this change of state some cancer cells break down due to strong mechanical stress, releasing their DNA. This represents a very strong inflammatory signal, potentially capable of activating the innate immune system. We therefore think that it can be exploited to enhance immunotherapy. In general, breast cancer responds little to immunotherapy, and for this reason it is defined as a ‘cold’ tumor, and we could instead have the opportunity to turn it into a ‘hot’ tumor”.
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Do all breast cancers behave this way?
“No. Think of tumors diagnosed early, when they are still in situ, what we call intraductal carcinomas, which develop and proliferate within the confines of the mammary gland duct. We know that only 30% of these have the ability to invade the tissues, become invasive and give rise to metastases, while for the remaining 70% of cases it is kept at bay by other healthy cells, and often regresses spontaneously.The point is that, today when we find ourselves faced with one of these tumors , we don’t know how it will behave and consequently we always resort to surgery and therapies. We need to find reliable markers to distinguish them. In our studies we have found that the RAB5A protein induces the fluidization of the tumor mass and is frequently expressed in remarkable precisely in the most aggressive breast tumors.We are trying to understand if this protein, together with physical and geometric characteristics, can be the scorer we seek”.
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However, we know that metastases can also form in other ways. Another Israeli research, for example, is focusing on invadopodia. What is it about?
“It’s true: the tumor uses very diversified strategies to survive and spread, which are often activated simultaneously, in order to bypass the body’s defenses. Invadopodia – also called invasive feet – are adhesive structures that the cell uses to escape from the matrix in which it is ‘imprisoned’. They are like a machine that serves to degrade, dig holes and channels. In general, however, now that we have learned more about cancer, most research focuses on the possibility of exploiting the immune system Studies on mRna vaccines, for example, fall into this vein”.
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In past years there has also been much talk of cancer stem cells as the only ones capable of spreading and giving rise to metastases. What do we know today?
“To give metastases, the tumor must be able to self-regenerate, and this ability is typical of stem cells. However, it has been discovered that many adult tumor cells can ‘go back’ and take on the same properties typical of stem cells. Also This has led us to change our perspective on cancer research.”