EACR 2016
Physical pressure of tumour on healthy cells induces oncogenes
Dr Emmanuel Farge - Institut Curie, Paris, France
What I presented today were experiments showing that the mechanical strains that are developed by tumour growth can activate biochemical pathways that are tumorigenic, that are dangerous in fact, in healthy tissues surrounding the tumour. So this is a kind of mechanical contamination of the healthy tissue by the tumorous tissue which is unusual because classically people and research found that molecules have to be secreted produced by the tumours and diffuse into the healthy tissue and it can eventually activate tumorigenic pathways and tumorigenesis in healthy tissues thanks to the signals. In our case what we found is that in addition to these biochemical signals that are associated to molecules that diffuse, there are also mechanical signals in terms of the pressure developed by the tumours compresses healthy tissues and this compression activates tumorigenesis in this tissue. So it transforms the healthy cells into hyper-proliferative cells, cells that begin to divide too much and eventually in certain cases it leads to also tumorigenesis in these cells.
What methodology did you use?
It’s fundamental research so it means that we found a new way for which tumour progresses. So it means that it had also new targets to fight against with pharmacological approaches, chemical approaches and eventually chemical treatment approaches. But this is not yet what we are doing. It’s really fundamental research, it opens to new possibilities to cure cancers hopefully in typically ten years or something like this.
What is the clinical importance of your research?
We are not thinking of this process as purely mechanical but what happens, in fact, in the cells, healthy cells that are compressed, is that the mechanical deformation changes the biochemical state of certain proteins because it’s easy to change the conformation, the shape, of the protein in response to mechanical strain. Changing the shape of a protein or conformation of a protein can eventually activate this protein and then activate a classical pathway which is biochemical. So the goal would be eventually… not eventually, the goal will be to treat chemically this process, meaning that you could try to inhibit chemically the mechano-sensitive pathways and see if it helps to fight against tumour growth. So you can use chemicals against mechanical induction because mechanical induction mixes mechanics and biochemistry so you will attack, you will try to inhibit the mechano-transitive pathways.
What technologies and techniques are you using in your research?
The technology is a bit unusual. We are, in fact, a consortium of different teams in Paris, the centre of Paris, and we are aggregated around Institut Curie which is an institute in which physics and biology cross-talk together very much since more than ten years now, twenty years. In fact, what we did within in this context is to use tools of chemists who produced magnetic liposomes and what you can do is to inject these magnetic liposomes into the blood and you can put a small magnet in front of the organ of interest you’re working on, in our case it’s the colon, and this in fact helps the liposomes to escape the blood flow and what we say is that it extravasates, it goes out from the blood, and then it can incorporate into the colon tissues. It’s very stable for weeks to months in mice and then you can use the magnet, which is localised in front of the colon, also to apply mechanical strain to the colon which is magnetised. Luckily, in fact, we could mimic quantitatively the tumour growth pressure thanks to these tools. So we could apply for weeks to months what is in fact the pressure developed by a tumour but without the tumour so we’re sure. What we do is entirely mechanical, it’s really the mechanical pressure that activates all these tumorigenic pathways independently of any biochemical molecules that would be secreted by a tumour. So the tools we are using were designed to test the role of this parameter, this mechanical parameter, in tumorigenesis.
