The LOX enzyme – Preparing the ground for cancer spread

Like seeds spreading in a garden, cancer cells need to land in the right environment to grow

Halting the ability of cancer to spread through the body (metastasis) is probably the major challenge facing researchers today. If the disease didn’t spread, it would be relatively easy to treat using surgery.

In the same way that rogue seeds spread dandelions across a lawn, cells break off from the original tumour and start growing in organs like the brain, lungs or liver. And once this has started, it’s much more difficult to treat the cancer successfully, and metastasis is responsible for around nine out of ten cancer deaths.

But just as seeds need fertile ground to flourish, there’s growing evidence that spreading cancer cells need the right ‘soil’ in which to grow. Scientists from the US, Canada and the UK have now discovered an important protein involved in preparing this biological ground, which points to a potential way to stop the spread of cancer.

The ‘pre-metastatic niche’

In 2005, a team of researchers in New York discovered that cells derived from the bone marrow could move into organs such as the lungs and form little clusters. These areas – known as ‘pre-metastatic niches’ – provide the fertile ground that spreading cancer cells need.

Writing in this week’s edition of the journal Cancer Cell, Janine Erler and her colleagues (including Cancer Research UK-funded scientists at the Institute of Cancer Research) have found that a protein called LOX plays a vital role in setting up these niches.

LOX – or lysyl oxidase, to give its full name – is an enzyme that sticks together proteins surrounding cells. It is also produced in relatively high levels by tumours. Could this be the key step in preparing the ground for cancer spread?

Studying LOX

First, Erler and her team carried out experiments in which mice were either transplanted with ‘normal’ breast cancer cells, or breast cancer cells that had been genetically engineered to lack LOX.

The results were clear – the mice carrying cancer cells lacking LOX had far fewer secondary tumours than those with standard cancer cells. And without LOX, cancer cells also failed to attract the bone marrow-derived cells that are crucial for cancer spread.

Furthermore, injections of purified LOX led to recruitment of bone marrow cells. And blocking LOX with antibodies prevented it. The researchers also showed that LOX was acting by “gluing” together proteins in the jelly-like matrix that surrounds cells. This helps to trap bone marrow-derived cells in the lungs, in turn providing the right environment for cancer cells.

But is this just a quirk of breast cancer cells grown in the lab? Maybe not, because the scientists then looked at 95 samples of secondary tumours taken from patients with a range of cancer types including breast, bowel, stomach and oesophagus. In more than half of the samples, the researchers found clusters of bone marrow-derived cells, along with high levels of LOX.

This is just the first step in a very long road to a potential new treatment for cancer, but it’s certainly exciting stuff. We now have a target that we know plays a crucial role in preparing the ‘soil’ for the ‘seeds’ of cancer spread. So the hunt is on to find ways to block LOX, and we look forward to hearing more about it in the future.

Kat