13 June 2017
A team of cancer researchers has developed an innovative new approach to exploring the extracellular matrix – the ‘web’ of molecules that surrounds and organises the cells in the body. The findings are published today in Nature Medicine.
The research team devised an intuitive new way to dissolve cells away from tissues, leaving behind the delicate three-dimensional architecture of the extracellular matrix (or matrix). The research was led by Professor Janine Erler (Biotech Research and Innovation Centre, University of Copenhagen).
The matrix surrounds the cells in every organ of our bodies, providing order, shape and structure and defining the environment within which cells exist. The matrix has a profound impact on how cells behave, and can help drive the progression of diseases such as cancer.
“In cancer, the way that tumour cells behave is powerfully influenced by the structure and composition of the surrounding matrix– and we also know that the matrix is crucial in enabling metastases [secondary cancers] to take root in distant sites in the body,” says Dr Thomas Cox (Garvan Institute of Medical Research).
Dr Cox, who now leads the Matrix and Metastasis group within Garvan’s Cancer Division, was previously at University of Copenhagen. There, he worked with Professor Erler and others, including Drs Alejandro Mayorca-Guiliani and Chris Madsen, to develop the new approach.
The researchers devised a new technique called ISDoT (in situ decellularisation of tissue) to dissolve cells away from tissue. Developed in mice post mortem, ISDoT is the first technique to use existing blood vessels to deliver cell-removing compounds directly to a specific tissue or organ.
“With this approach, we avoid collapse of the delicate matrix architecture – and we can also successfully remove all of the cells from tumours, which is particularly difficult because they are typically denser than normal tissue,” Dr Cox says.
“When you remove the cells, the clarity of what you can see through the microscope is much greater. Not only can you see the fibres of the matrix more clearly, but you can look much deeper into the tissue.
“And because we’re removing the cells completely, we can also use mass spectrometry to catalogue the components of the matrix – in normal tissue and in tumours – in great detail.”
By using ISDoT to dissolve away cells, the team has investigated the matrix of normal tissues, and shown how its organisation can change over the course of tumour development and metastasis.
Among other findings, the team has shown that the components of the matrix in secondary tumours differ markedly between tissues.
“We have looked at metastatic tumours in the lung and in the lymph node, and we see important differences between them in terms of the molecular makeup,” Dr Cox says, “That’s telling us that remodelling of the matrix in cancer is organ-specific – and that could be important in the future in the development of therapies to target the matrix.”
Dr Cox says the new approach is already making waves among cancer researchers.
“Other researchers are saying to us at conferences [where we present our findings], ‘I’ve never seen this kind of structure before – what does it mean?’ And we don’t always know, we’re still learning – because we’re seeing things that no one has seen before.”
“This is remarkable work that has broad implications for cancer research. Undoubtedly, other research groups around the world will adopt this technology to advance their own work in understanding cancer and other diseases,” says Professor David Thomas, who heads Garvan’s Cancer Division and The Kinghorn Cancer Centre.
“We’re delighted that Thomas Cox – who contributed substantially to this study – has come to work with us here at Garvan and is bringing his great expertise and technical knowhow with him.”
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