Scientists studying the pigment cells – the melanocytes – in the skin have identified a protein, the loss of which is critical to making these cells cancerous. When cancerous ('malignant melanoma') pigment cells are forced to make this protein again in the laboratory, announce Alan N. Houghton and colleagues from the Memorial Sloan-Kettering Cancer Center, New York in the United States, the cells resume their normal appearance and lose their ability to form a tumour.

As Houghton and his team report in the Journal of Experimental Medicine [August 1999], the protein concerned is known as DPPIV (dipeptidyl peptidase IV). DPPIV normally sits on the surface of healthy skin pigment cells, but disappears from these melanocytes as soon as they become malignant.

Houghton's group found that, when human melanoma cells lacking DPPIV are genetically engineered to produce the protein again, they revert to more normal melanocyte behaviour; and, when injected into mice, these DPPIV-producing cells no longer cause tumours.

Cells undergo many changes in the proteins they make when they transform into cancer cells. Some of these alterations can make a cell produce something it doesn't normally produce; others can stop it producing one of its usual proteins. One of the tasks of the cancer biologist is to find out which of these changes genuinely contribute to malignancy and which are simply by-products of the process.

The change in DPPIV is of particular interest as it is thought to play a role in making melanoma cells able to survive and grow independently of the growth factors melanocytes usually need – the supply of which is strictly regulated by the body. This independent growth is one of the crucial stages in the development of a cancer cell, as it enables the cell to elude one of the main controls exerted by the body on unwanted cell multiplication.

When Houghton and his group investigated the 'cured' melanoma cells they found that, along with re-acquiring the ability to produce DPPIV, they had also re-acquired a reliance on growth factors.

DPPIV is a polymath of a protein. One of its functions is as a 'protease', a biological catalyst or enzyme that can break down other proteins. Hence, one explanation for why DPPIV is required for normal growth control is that it may limit cell multiplication by destroying growth factors as soon as they come into contact with a cell. If this is the case, it is easy to see why its loss has such catastrophic effects.

But cancer cells are never that simple. The researchers also found that, although DPPIV's protease activity was essential for the cells to lose their ability to form tumours, it was not needed to bring the cells back under growth factor control. The presence of DPPIV seemed to be enough

And this is where the melanoma cell starts to resemble a Russian doll, which when opened reveals yet another doll inside. For the loss of DPPIV that occurs in melanoma cells also leads to the disappearance of another cell-surface protease. When the DPPIV reappears, this other enzyme reappears as well; and this, Houghton speculates, may be what is actually keeping the growth factors in check.