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New cancer finding

Wednesday 17 December 2008

The Daily Telegraph has reported that, “scientists have discovered how cancer spreads around the body raising the possibility it could be stopped.” It said the researchers have found an enzyme that is necessary for breast cancer cells to spread around the body and by blocking it the cancer cannot spread. The newspaper said that although the work is in its early stages, the researchers describe it as “exciting” and that by stopping it from spreading, “you stop cancer from killing people”.

This research is at an early stage but offers a potential new avenue for drug development research. The findings will be of great interest to other researchers working in this area. Although no drugs that specifically block this enzyme are currently known, if such drugs could be identified and were proven safe in humans, then the newspaper’s claims could be realistic. However, much more research is needed to determine if this is the case.

Where did the story come from?

Dr Gianluca Sala and colleagues from research departments at the University of London and the Universities of Milan and Chieti in Italy, carried out this research. The work was supported by grants from the Association for International Cancer Research and the European Commission. The study was published in the peer-reviewed journal Cancer Research.

What kind of scientific study was this?

This laboratory study was aimed at investigating cancer metastases and the enzymes that determine how they spread. Metastases are the secondary tumours that form in distant parts of the body when a primary tumour or cancer spreads. There are several steps to this process: cells first invade local tissues, then move out into the blood stream, then move through the body before settling and establishing themselves with new blood supplies in distant sites.

Previous research has indicated that the movement, or migration, of breast cancer cells is one of the activities thought to be controlled by the enzyme phospholipase Cg1 (PLCg1). Enzymes are protein molecules that control biological or chemical reactions. To investigate cancer metastases spread, the researchers carried out several laboratory tests in mice and human breast cancer tissue.

The researchers state that they have developed a method by which they can make human breast cancer cells grown in the laboratory reduce the amount of PLCg1 they produce (called down-regulating PLCg1). Part of the study involved them testing the effect that down-regulating PLCg1 had on human breast cancer cells in the laboratory.

The next part of the experiment took place in seven-week-old mice that had been genetically engineered to have a deficient immune system that allows cancers to grow. The mice were injected with human breast cancer cells with either normal or down-regulated PLCg1 levels under conditions that allowed the cancer to move to the lungs. The mice’s lungs were examined for metastases after five weeks.

To see what would happen if they allowed the lung tumours to grow before down-regulating PLCg1, the researchers repeated this experiment using cancer cells that were genetically engineered so that they only down-regulated PLCg1 when treated with the antibiotic tetracycline. The researchers injected mice with these cancer cells and left them for 14 days, by which time metastases would have had a chance to form. After this, half of the mice were treated with tetracycline to down-regulate PLCg1, and half left untreated. After 46 days, the researchers then looked to see how many mice from the treated and untreated groups had lung metastases.

Other mice were injected with tumours directly under the skin and the growth of these tumours was measured twice a day for 35 days with or without down-regulating PLCg1. Finally, the researchers looked at the levels of PLCg1 enzyme in samples of human primary breast cancers and in lymph node metastases from these breast cancers.

What were the results of the study?

The researchers state that they have shown the enzyme PLCg1 to be an important enzyme in the development and maintenance of cancer metastasis. They found that reducing the amount of the enzyme PLCg1 in human breast cancer cells reduced their ability to move and “invade” tissue-like material in the laboratory.

This was also demonstrated by the finding that all mice injected with human breast cancer cells with normal levels of PLCg1 developed metastases in their lungs, compared to only 20% of mice injected with PLCg1 down-regulated breast cancer cells. If the researchers down-regulated PLCg1 after lung metastases had time to form, this seemed to cause remission of lung metastases, as they were not visible in five out of the six mice treated in this way, while four out of five control mice had lung metastases.

The researchers noted that down-regulating PLCg1 had little effect on the growth of the primary tumour. Finally, they found that there was less PLCg1 enzyme in human primary breast cancer tumour than in lymph node metastases from these breast cancers.

What interpretations did the researchers draw from these results?

The researchers say that their results strongly suggest that PLCg1 inhibitors may have potential therapeutic applications for the clinical treatment of cancer metastasis. They confirm that there are currently no specific PLCg1 inhibitors available and therefore a need to develop them.

What does the NHS Knowledge Service make of this study?

This laboratory study will be of great interest to other researchers working in this area. The researchers have identified an enzyme involved in the regulation and control of cancer spread. They hope that blocking or inhibiting the enzyme will be a potential avenue to explore in designing drug treatments. Although the researchers succeeded in down-regulating the enzyme in cancer cells in the laboratory using genetic manipulation, they have not yet been able to find a drug that matches this result. As such, this line of investigation should be considered as early research.

Sir Muir Gray adds...

Any drug developped from this field of research might not necessarily be a cure, but it could have an important role to play.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Scientists may be able to stop cancer spreading round the body.

The Daily Telegraph, 17 December 2008

Links to the science

Sala G, Dituri F, Raimondi C et al.

Phospholipase C 1 Is Required for Metastasis Development and Progression.

Cancer Research 2008; 68, 10187-10196