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Breast cancer enzyme may slow tumour growth

Friday 24 May 2013

"Cancer cell enzymes shown to act as 'good cops'," is the headline on the BBC News website.

The BBC reports on laboratory research into an enzyme called MMP-8 and its effects on breast cancer. The research reveals that while MMP-8 appears to stimulate the growth of breast cancer cells in the short-term, it may slow tumour growth in the long-term.

Scientists are likely to want to explore new treatments that use MMP-8’s ability to slow tumour growth in this way. However, this study used laboratory-grown cells, which don’t behave in the same way as tumour cells within the body. It could be the case that the effect of MMP-8 is different when studied in people.

Nonetheless, this research provides new understanding about how the MMP-8 enzyme influences the growth and development of laboratory-grown breast cancer cells. And while this research has limited immediate implications for people with breast cancer it does contribute new understanding that may help to treat the disease in the future.

Where did the story come from?

The study was carried out by researchers from the University of East Anglia (UK) and the University of Vermont College of Medicine (USA) and was funded by Breast Cancer Campaign, Cancer Research UK, the European Union Framework Programmes 6 and local Norfolk fundraisers.

The study was published in the Journal of Biological Chemistry, a peer-reviewed science journal. It was published as an open-access article so it is free to download.

The reporting of the research was mixed. While the Mail Online exaggerated the results of the study by describing a “breakthrough” that “turns previous thinking on its head”, the BBC coverage was more restrained, including comment from Cancer Research UK on how the research provides "very early clues" about how the enzyme might recruit cells to fight breast cancer.

What kind of research was this?

This was a laboratory study exploring the role of an enzyme called matrix metalloproteinase-8 (MMP-8) in the growth of breast cancer tumour cells.

MMP-8 performs many essential jobs in a normal cell. The researchers say it is known to activate certain immune system signals (called interleukin-6 and interleukin-8), which are types of molecules that regulate and orchestrate the actions of the immune system.

The researchers comment that, traditionally, scientists thought MMP-8 helped cancer cells grow and spread, but more recent research has suggested it may also prevent cancer cell growth.

This research sought to find out if, and how, MMP-8 inhibited tumour cell growth in laboratory-grown breast cancer cells.

Understanding the biology and chemistry of processes involved in diseases such as cancer through laboratory studies is essential if we want to discover new ways to prevent and treat them.

What did the research involve?

The researchers grew human breast cancer tumour cells in a laboratory. Some cancer cells were deliberately engineered to lack a properly functioning MMP-8 enzyme (called “mutant MMP-8”), whereas others had a fully functional version (known as the “wild-type” version). The intention was to see what effect this had on the ability of the cancer cells to grow and develop.

The researchers paid particular attention to the effect of this manipulation on the immune system signalling molecules interleukin-6 (IL-6) and IL-8, which are known to be involved in the growth and development of cancer cells. Genetic changes within the cells were also measured. 

All the research was carried out in artificially grown laboratory cells and no tests were done in people with cancer.

What were the basic results?

The research found tumour cells containing the wild-type MMP-8 had elevated levels of IL-6 and IL-8 and that, in the short-term, this was associated with higher levels of tumour cell growth. Cells lacking a working MMP-8 enzyme had lower levels of IL-6 and IL-8 and did not grow as well.

However, in the longer term, activity of the MMP-8 enzyme was found to inhibit the growth of the tumour cells and it was found that the IL-6 and IL-8 levels were no longer elevated.

Interestingly, the small number of cells with a working MMP-8 enzyme that did keep on growing in the long-term had somehow maintained their elevated levels of IL-6 and IL-8 but these were no longer dependent on MMP-8 activity. The relationship had changed from the short- to the long-term.

This showed that in the early stages of tumour growth MMP-8 activity stimulated IL-6 and IL-8, which helped the tumour grow, but, later on, MMP-8 activity limited tumour growth and the IL-6 and IL-8 levels returned to normal.

Only cancer cells where MMP-8 activity had become disconnected from IL-6 and IL-8 levels were able to keep growing in the longer term. 

How did the researchers interpret the results?

The researchers concluded that their research showed a “causal connection” between “MMP-8 activity and the IL-6/IL-8 network”, which showed MMP-8 influences the signalling of pro-inflammatory factors (IL-6 and IL-8) that “conventionally promote tumour cells’ growth and development”.


This laboratory study provides new understanding about how the MMP-8 enzyme interacts with inflammatory signals (IL-6 and IL-8). MMP-8 might be something of a double-edged sword. While it stimulates the growth of cancerous cells in the short-term, it may also suppress growth in the long-term.

As with all laboratory studies, new or different discoveries need to be replicated by other research groups to ensure they are accurate and the results weren’t due to chance.

Assuming the research results are valid they could provide an opportunity for cancer researchers to investigate and possibly devise new methods of using MMP-8 activity to supress breast tumour cell growth. However, the research found that some tumour cells kept growing despite the presence of MMP-8. This highlights that cancer cells differ, and that, often, what works in one place and setting may not work in others.

It is important to remember that the researchers investigated breast cancer cells only, so this study alone does not tell us anything about the role of MMP-8 in other cancer types. Similarly, the research used artificially grown breast cancer cells, which may not behave in exactly the same way as tumour cells within a human body.

This research into a new target for drug development provides new and interesting understanding that other researchers can build on. An improved understanding of the biology underpinning breast cancer may lead to the development of new treatments.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Cancer cell enzymes shown to act as 'good cops'

BBC News, 24 May 2013

Breast cancer cells can suppress tumour growth 'by releasing protective proteins'

Mail Online, 24 May 2013

Links to the science

Thirkettle S, Decock J, Arnold H, et al.

Matrix metalloproteinase-8 (collagenase-2) induces the expression of interleukins-6 and -8 in breast cancer cells

The Journal of Biological Chemistry. Published online May 30 2013