Enzyme reduces cancer spread
The spread of cancer to other organs has been reduced in mice by blocking an enzyme. Researchers blocked the enzyme LOXL2 in mice using chemicals and genetic engineering techniques.
While this did not slow the rate of the tumour growth, it did reduce the spread of the cancer to the liver and lungs.
The findings could lead to the development of medicines that stop the spread of cancer to other organs. The enzyme could also be used to test whether cancer is likely to spread in patients and so predict patient outcomes.
The spread of cancer to other parts of the body, called metastasis, is responsible for nine tenths of cancer deaths. Around 47,000 new cases of breast cancer are diagnosed in the UK each year and around 12,000 patients die from the disease. Analysing tissue samples from patients with breast cancer, researchers found that high levels of the enzyme LOXL2 were linked to cancer spread and poor survival rates.
Researchers injected mice with two different types of breast cancer cells which then grew into tumours. One cell type produced high levels of LOXL2, while the other had been genetically modified to inhibit production of LOXL2. They found that tumours grew at a similar rate in mice regardless of the level of LOXL2 in the injected cancer cells. This suggests that LOXL2 is not required for tumour growth. However, mice injected with tumour cells with low levels of LOXL2 had fewer secondary tumours in the lung or liver.
Researchers found that LOXL2 helps cancer cells to invade surrounding tissue by controlling levels of molecules called TIMP1 and MMP9. These molecules have previously been shown to play a role in metastasis.
Researchers also genetically modified mice to produce breast tumours early on in their life. After four weeks, they injected the mice with a chemical called D-penicillamine, which inhibits LOXL2. There was no difference in tumour size between mice that had been injected with D-penicillamine and those which had not. However, those treated with the chemical had fewer secondary lung tumours.
Delaying treatment with D-penicillamine until five weeks resulted in no difference in the number of secondary lung tumours. This suggests that LOXL2 is only important in the early stages of metastasis.