The skin is a protective physical barrier and because it is continually exposed to the environment it needs to keep regenerating in order to function. In fact, each person completely replaces all of their skin in a period of less than two weeks. To maintain this process, the skin contains stem cells which are responsible for producing all the cellular components, such as keratinocytes, sebaceous glands and hair. Alterations in the function of these stem cells can impair the maintenance of the skin's integrity and can even lead to tumours if they begin to proliferate uncontrollably.
Scientists at the Cancer Research Centre, which is run jointly by the Scientific Research Council and University of Salamanca, have identified two proteins that modulate the way these stem cells behave. A group led by Xosé Bustelo has discovered that the Vav2 and Vav3 proteins are key to ensuring that there are sufficient stem cells in the skin and that they function properly.
Any alteration in that function favours the appearance of skin tumours, so this finding, which has been published in the Oncogene journal, may help to develop new anti-tumour therapies.
During their experiments with genetically modified mice, the scientists discovered that when these two proteins are eliminated fewer stem cells are produced, and those that exist do not function properly.
“This resulted in defective skin regeneration processes after suffering wounds or after depilation,” the experts have explained. On the other hand, when these molecules were chronically activated there was an increase in the stem cells and the skin regeneration processes were much faster.
“The activated form of these proteins behaves like natural hair growth; it led to increased hair formation when skin regeneration was induced in the mice. Wounds also healed more quickly,” said researcher Francisco Lorenzo-Martín.
However, when they caused tumours, these activated stem cells also produced more malignant characteristics. "By studying this process we have been able to develop new diagnostic signatures that predict the evolution of skin cancer patients and, at the same time, look at new ways to deactivate these malignant functions," explained Xosé Bustelo.
Microchip analysis of normal and tumour stem cells to evaluate the changes has given the scientists a greater understanding of the mechanisms regulated by Vav2 and Vav3 which are associated with these physiological and malignant functions. This, in turn, has allowed the development of new diagnostic signatures, as well as targeting molecules which are of interest as therapies against skin cancer.