British scientists have started work on a revolutionary construction project: building a tumour from its basic biological components.
While the idea of building rather than destroying a tumour might seem perverse, the aim is to understand how cancers develop and how they spread through the body. To achieve this ambitious goal, the researchers based at Barts Cancer Institute in London have taken tissue from ovarian cancer patients and stripped these samples down to their constituent components. Now they are using these to try to rebuild a tumour from scratch.
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The project, known as CanBuild, has been funded through a £1.78m grant from the European Union and Cancer Research UK and is intended to provide insights into the complex process by which cancers develop. In the wake of this work, improved tumour treatments could be created, say researchers.
Work on CanBuild began in 2013 and is expected to be completed in two years. However, preliminary results will be unveiled early in July in a special display of the team’s work that will form a part of the Royal Society’s summer exhibition in London.
“It is common to think of cancers as being simple balls of malignant cells,” said project leader Prof Fran Balkwill. “But that is not the case. Only about half the cells that make up a tumour are actually cancerous. Other non-malignant cells that are found in a tumour include immune cells such as macrophages, lymphocytes, fibroblasts, endothelial cells, fat cells and many more. A tumour is really an entire organ – a rogue organ, more precisely – that has acquired its own blood vessels and structure thanks to the additional cells it has acquired.”
Crucially, these additional cells are not actually grown by the cancers themselves. They are suborned from surrounding healthy tissue.
Then, after they are recruited by the cancer, they are corrupted by it in order to help it develop. “These are cells that have been turned to the dark side,” said Balkwill.
A cancer is triggered when genetic switches within a cell – for example, a cell from a lung or from breast tissue –are turned on, causing it to divide uncontrollably. Fail-safe mechanisms within the cell normally stop or hold back this process of unbridled self-replication. However, on occasions, these defence mechanisms fail and a tumour begins to form.
“At the very start, when the tumour only consists of a few malignant cells, genes are turned on inside their nuclei,” said Balkwill. “These genes direct the cells to make chemicals that are known as cytokines and chemokines – and these chemicals are responsible for recruiting all the other cells that go to make up a tumour.”
Among the cells that are drawn into the growing cancer by these chemical messengers are fibroblasts which manufacture the matrix that provides tissue with its structure. Others include lymphocytes, dendritic cells, natural killer cells and macrophages which are normally involved in the body’s immune defences. By subverting these cells to its cause, the cancer suppresses the body’s immune responses and so manages to escape detection and attack.
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In addition, cells that facilitate the development of blood vessels are drawn into the emerging cancer, supplying the newly created cancer with a source of energy – as well as material to create a structure for itself and to provide defences against immune attack.
Balkwill believes that this whole complex process is driven by the initial malignant cell. It is not an inherent property of the tissue in which the tumour first arises, she insists. “The idea is controversial, I admit, but I believe it is right,” she added.
Having isolated the various building blocks that are suborned to make a tumour, Balkwill and her colleagues are now trying to put them back together to create one. “We have taken ovarian tumours and analysed their composition and now we are trying to put together those pieces in order to create one tumour. Essentially we have deconstructed a tumour and now we are going to try to reconstruct one.
“The crucial point is that in putting one together – which we will do in the laboratory – we learn so much about a particular tumour, we hope that we will be able to find ways of blocking or disrupting that process in the human body.”