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Potential treatment for melanoma

Friday 8 February 2008

Melanomas could be treated using an “anti-tumour protein”, reports The Guardian , adding that the protein “puts cells into hibernation or makes them commit suicide if they start to get cancerous”. This research “could be used as a new way to threat the notoriously aggressive cancer”, the article adds.

The news item is based on laboratory research in cells and in mice, which investigated what caused cells with a particular gene mutation to become cancerous. The researchers discovered that a protein – IGFBP7 – prevents the cells from dividing uncontrollably. The researchers found that when mice with human melanoma tumours were injected with the protein, the tumours stopped growing. However, as with all animal studies, the effects of the protein on malignant melanoma will need to be tested in humans. Until that is done it is impossible to tell whether the protein is effective and safe in the treatment of melanoma.

Where did the story come from?

Dr Michael Green and colleagues from the Howard Hughes Medical Institute and Boston University School of Medicine carried out the research. No sources of funding were reported. It was published in the peer-reviewed scientific journal: Cell .

What kind of scientific study was this?

This was an experimental laboratory study in human and animal cells grown in the laboratory, and in mice. About 70% of human melanomas have a mutation in the BRAF gene, however, this mutation is also found in about 80% of non-cancerous moles. The researchers were interested in looking at why some cells with the mutation become cancerous, while others lose the ability to divide or they die by committing “cell suicide” (apoptosis). One theory that explains the difference between the cells is that is that the cells that undergo uncontrolled division have another gene mutation which stops them from either losing the ability to divide or from committing suicide.

The researchers took human foreskin cells grown in the laboratory and introduced a mutated BRAF gene into these cells. They then looked for cells that began to undergo uncontrolled division. Once the genes responsible had been identified, the researchers then repeated the experiment in human melanin-producing cells to confirm their findings. They then tested the cells to see whether the genes they had identified were involved in apoptosis or loss of the ability to divide.

The researchers were particularly interested in one of the genes, IGFBP7 , which produces a protein that is secreted by the cells. They thought that this protein might act as a signal to cause the cells to lose the ability to divide or to commit suicide. They tested this by looking at the effects of adding the liquid that cells with the BRAF mutation were grown in to other cells that did not have the mutation. They then looked at the effects of removing the IGFBP7 protein from this liquid.

The researchers also looked at whether human melanoma cells grown in the laboratory produced IGFBP7, and whether exposing them to this protein stopped them dividing. They then injected mice with human melanoma cells, either with or without the BRAF mutation, and three, six, and nine days later they injected the mice with either IGFBP7 or a control solution without IGFBP7 to see what effect it had.

What were the results of the study?

The researchers identified 17 genes that caused cells containing the BRAF mutation to divide uncontrollably when their activity was reduced. Almost all of these genes (16 of the 17) were involved in the process of cells losing the ability to divide (senescence), and three of these genes were involved in the cells committing suicide (apoptosis). One of the genes that played in role in senescence and apoptosis was IGFBP7 , which produces a protein that is secreted by the cells.

The researchers found that if the liquid that cells with the BRAF mutation were grown in was added to other cells that did not have the mutation, they went into senescence. The liquid did not have this effect if they removed the IGFBP7 protein.

Human melanoma cells that had the BRAF mutation did not produce IGFBP7, and if they were exposed to it, it stopped them proliferating and caused them to die by committing cell suicide. In mice with human melanoma tumours, injecting IGFBP7 into the tumour site or into the general circulation stopped the tumours from growing.

What interpretations did the researchers draw from these results?

The researchers concluded that loss of activity of the IGFBP7 gene allows human melanin producing cells with a BRAF mutation to develop into cancerous melanoma cells. IGFBP7 might be useful for treating malignant melanomas that have a BRAF mutation. 

What does the NHS Knowledge Service make of this study?

This was a complex and thorough study. Its results are promising, but the effects of IGFBP7 on malignant melanoma will need to be tested in humans before it is possible to say whether it will be a safe and effective treatment.

Sir Muir Gray adds...

Promising results in mice; but the probability of success in humans needs further testing, and may, as with all animal tests, not be able to be reproduced in humans.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

'Suicide protein' could help treat melanomas.

The Guardian, 8 February 2008

Links to the science

Sasse AD, Sasse EC, Clark LGO, et al.

Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma.

Cochrane Database Syst Rev 2007, Issue 1

Crosby T, Fish R, Coles B, Mason MD.

Systemic treatments for metastatic cutaneous melanoma.

Cochrane Database Syst Rev 2000, Issue 2

Wajapeyee N, Serra RW, Zhu X, et al.

Oncogenic BRAF Induces Senescence and Apoptosis through Pathways Mediated by the Secreted Protein IGFBP7.

Cell 2008; 132: 363–374