How dissolving cells reveals cancer secrets

A new technique shines a light on the extracellular matrix, the scaffolding that holds your cells, gives tissue its structure, and plays a key role in the spread of cancers. Anthea Batsakis reports.

A decellularised mouse mammary gland, stained to show collagen IV, an important molecule in the extracellular matrix.
A decellularised mouse mammary gland, stained to show collagen IV, an important molecule in the extracellular matrix.
Erler lab

The microscopic structure of tumours has always remained somewhat elusive for biologists. But thanks to a new technique, scientists have, for the first time, seen in three dimensions the “net” that holds our cells in place and gives tissues their shape, known as the extracellular matrix.

Led by Janine Erler from the University of Copenhagen, where the research took place, this technique may help reveal the architecture of tumours and explain why tumours can grow back in different parts of the body after being removed.

Until now, studying the extracellular matrix required tissue to be sliced into tiny strips and dropped into a beaker of solution – at best, this technique showed the matrix in two dimensions.

In research published in Nature Medicine, the scientists instead used blood vessels to transport cell-removing compounds into mouse organ tissue, gently dissolving the cells and hollowing out the organ to leave behind its delicate scaffolding. They call the technique in situ decellurisation of tissue, or ISDoT.

The fibres of the extracellular matrix, made up of a complex lattice of proteins and carbohydrates secreted from cells, can be seen with far greater clarity without the cells obstructing the view.

Thomas Cox, one of the authors of the paper, is a cancer cell biologist from the Garvan Institute in Sydney, Australia. “We’ve seen things that we never would have expected and we don’t know exactly what they mean, but that’s all part of the fun,” he says.

“No has ever seen this before and we’ve got plenty to keep us busy to follow up on.”

As well as giving physical structure to our tissues, the extracellular matrix also has a powerful influence on cell behaviour.

When it comes to tumours, the extracellular matrix and cancer cells manipulate one another. Cancer cells, for instance, can create more of the matrix, destroy it and remodel it.

“This is why our study is important, because it has been shown that as cancer cells change their environment, they’re more able to go on and multiply uncontrollably,” Cox says.

Using mass spectrometry, Cox and his colleagues identified and catalogued different components of the matrix. Interestingly, they found that the way secondary cancer cells (metastases) remodel the matrix is specific to the organ they’re growing within.

Queensland University of Technology breast cancer biologist Rik Thompson, who didn’t take part in the study, says the varying structure of the matrix in secondary tumours might be why they’re more difficult to treat.

“This is exciting in that it provides a robust, validated approach for examining extracellular matrix and already has shown some very new information,” Thompson says.

“The mass spectroscopy takes the study to a new dimension, with hundreds of proteins identified to vary in the extracellular matrix around cancers compared to the normal tissues.”

He adds that this new technique will influence his own research on how proportions of breast tissue plays into the risk of breast cancer.

“This approach would enable us to more comprehensively understand the structure and composition of the extracellular matrix in regions of high versus low mammographic density.”

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