LOX holds a key to curbing cancer's spread

[Guest guest]

A key molecule which is crucial for the spread of cancer has been identified by

US scientists. Blocking the protein stopped the spread of tumours in mice, and

the researchers hope it may offer a valuable target for cancer therapies in

humans.

 

The spread of cancer cells, or " metastasis " , is a major problem and the

principal cause of mortality among cancer patients. Now researchers at Stanford

University School of Medicine, California, US, headed by Amato Giaccia have

discovered the enzyme that mediates metastasis.

 

The potentially rampant spread of cancer through the body depends on a

number of factors (http://www.newscientist.com/article/dn3801.html) . But low

oxygen conditions are typically associated with the human cancer cells capable

of

spreading.

 

The researchers uncovered the enzyme responsible for the spread

of oxygen-starved cancer cells in human breast, head and neck cancers.

 

Dubbed LOX (lysyl oxidase), the enzyme is produced in cancer cells under low

oxygen conditions. The team found that human breast cancer cells lacking oxygen

produced more LOX. They also found that patients whose tumour cells made high

amounts of LOX were more likely to suffer metastasis and had a lower chance of

survival.

 

Lungs and liver

 

The team grew human breast cancer cells on artificial gels created to mimic the

natural environment in which these cells move in the body. Normal cancer cells

showed a branched appearance, typical of spreading cells. But cancer cells in

which the production of LOX was blocked using an inhibitor, failed to spread on

the gels.

 

They remained in spherical clusters showing little branching and were

completely immobile.

LOX is implicated in the invasiveness of tumoursâ€, says Giaccia. But it also

does another thing. As well as causing cells to spread, he believes LOX also

creates a “permissive niche†or environment which also boosts the cells’

growth so they multiply.

 

To test the therapeutic potential of LOX, the team engineered human breast

cancer cells to produce less LOX than normal cancer cells. They then implanted

these cells in the form of tumours into mice.

 

Hot target

In mice that received the normal tumours, the cancer cells spread to the lungs

and liver. But those that received the tinkered tumours producing less LOX had

fewer cancer cells in the lungs and none in the liver.

 

Furthermore, when a chemical inhibitor of LOX was given to mice harbouring the

normal tumours, metastasis was completely blocked. The team achieved the same

effect using an antibody that blocked the function of LOX.

 

“The findings are highly interesting since they create an entirely new set of

insights into the mechanisms of invasion and spread of cancer,†says Robert

Weinberg, a cancer biologist at the Whitehead Institute for Biomedical Research,

Massachusetts, US.

 

Although blocking LOX can block the spread of cancer, it does nothing to the

primary tumour itself, cautions Giaccia. “But since LOX is involved in the

early and late stages of the spread, it is a hot therapeutic target,†he

adds. The team is now developing human-compatible antibodies to block LOX.

Journal reference: Nature (DOI: 10.1038/nature04695)

 

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Weblinks

* _Stanford University School of Medicine_ (http://med.stanford.edu/)

* _http://med.stanford.edu/_ (http://med.stanford.edu/)

* _Cancer special report, New Scientist_

(http://www.newscientist.com/channel/health/cancer)

* _http://www.newscientist.com/channel/health/cancer_

(http://www.newscientist.com/channel/health/cancer)