New method unveil insights into cancer tumours – University of Copenhagen

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14 June 2017

New method unveil insights into cancer tumours

CANCER RESEARCH

Scientists from the Biotech Research & Innovation Centre (BRIC) at the University of Copenhagen have developed a groundbreaking method to reveal the structure of tissues and tumours with unprecedented detail. The method unveils new insights into the structure of tumours to help develop targeted therapies for cancer in the future

New research from University of Copenhagen gives us insights into how tumours and normal organs are built, and what their differences are. The researchers have developed a new epochal method that is an advance in the fields of both cancer research and bioengineering and it might even have an impact on organ regeneration and tissue engineering in the future.

We have developed a technique to obtain intact organ scaffolds and to image them in incredibly high detail using microscopes. We are the first to image the 3D structures of primary and metastatic tumours as well as healthy organs in this way”, says Professor Janine Erler from BRIC.

Understanding cancer progression

Our cells which are organised to form tissues rely on the extracellular so-called matrix. The matrix surrounds the cells in every organ of our bodies, and provides shape and structure to the organ. It has a profound impact on how cells behave, how to arrange themselves properly, and to sense how to behave when their environment changes. Sometimes this organisation goes wrong and cells grow into tumours. To destroy a tumour, it is essential to know both its structure and the foundation upon which it is built. Yet the matrix is extremely difficult to study in detail.

Now a team of researchers led by Professor Janine Erler has developed a new technique published in Nature Medicine this week that makes closer study of the matrix possible. The technique reveals the inner structure of organs and tumours by removing cells but leaving the matrix completely unaltered. The three-dimensional structure of this matrix has never been seen in such detail before.

We are now re-introducing cells into our extracellular matrix scaffolds, bringing them back to life, to study how tumours form and how cancer progresses. This is extremely exciting and offers a unique opportunity to study how cells behave in their native environment,” explains Professor Janine Erler.

The extracellular matrix structure revealed. A de-cellularised cancer growth. Image by Alejandro Mayorca-Guiliani.

A world of details revealed

The new method was pioneered by postdoctoral fellow Dr Alejandro Mayorca-Guiliani, in Professor Janine Erler’s team, who says, “We have isolated the structure that keeps tissues in place and organises the cells inside them. We did this by using existing blood vessels to deliver cell-removing compounds directly to a specific tissue to remove all cells within an organ. Doing this leaves behind an intact scaffold that could be analysed biochemically and microscopically, providing us with the first view of the structure of tumours.”

Imaging expert and co-first author Chris Madsen (now at Lund University, Sweden) says “When you remove the cells, the clarity of what you can see through the microscope is much improved – you can see the fibres of the matrix more clearly and you can look much deeper into the tissue. Using this approach, we have been able to see important differences in matrix organisation when we looked at metastatic tumours in the lung and in the lymph node.

Matrix Biology and mass spectrometry expert and also co-first author Thomas Cox (now based at the Garvan Institute of Medical Research, Sydney) says “Because we are removing the cells completely, we can use mass spectrometry to identify and catalogue the components of the matrix – in normal tissue and in tumours – in unprecedented detail. What is really exciting is we found that some of the components of the matrix in different secondary tumours [metastases] are unique to that tissue. That is telling us that remodelling of the matrix in cancer is organ-specific”.

The research is supported by the Danish Cancer Society, the Novo Nordisk Foundation, a European Research Council Consolidator Award, the Ragnar Söderberg Foundation Sweden, Cancerfonden Sweden, the Innovation Foundation Denmark, the National Health and Medical Research Council (NHMRC) Australia and the Danish Council for Independent Research.

For more information, contact:

Professor Janine Erler, BRIC, Janine.erler@bric.ku.dk

Lonnie Moldt Jørgensen, Communications Officer BRIC, lonnie.jorgensen@bric.ku.dk

Original article

“ISDoT: in situ decellularization of tissues for high-resolution imaging and proteomic analysis of native extracellular matrix”. Nature Medicine (2017). DOI: 10.1038/nm.4352.