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.
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 the journal Nature Medicine 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 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) said “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 metastases are unique to that tissue. That is telling us that remodelling of the matrix in cancer is organ–specific”.