The epidermis may be more resilient to cancer than previously thought and can still function even when a battle between mutated cells takes place within the skin tissue, according to a study published in Cell Stem Cell(Sept. 2018; S1934–5909(18):30402–8).
Researchers concluded that once mutated cells in the skin develop, they grow to form clones that compete against each other. In a process similar to the selection of species during evolution, several mutant clones are lost from the tissue while this competition takes place. At the same time, the skin tissue can function normally while being overrun by the clashing mutant cells.
“In humans, we see a patchwork of mutated skin cells that can expand enormously to cover several millimetres of tissue. But why doesn’t this always form cancer? Our bodies are the scene of an evolutionary battlefield. Competing mutants continually fight for space in our skin, where only the fittest survive,” said lead author Dr. Phil Jones, Professor of Cancer Development at the University of Cambridge, based at the MRC Cancer Unit, senior group leader at the Wellcome Trust Sanger Institute, and Honorary Consultant in Medical Oncology at Addenbrooke’s Hospital in Cambridge, in a press release.
Researchers from Cambridge University found that skin tissue can
function normally, while being a battleground of sorts for mutated skin cells.
Dr. Jones and his colleagues used a mouse model in their investigation. They focussed on the mutation of the p53 gene, a known driver in non-melanoma skin cancer.
The researchers created a genetic ‘switch,’ that upon activation, replaced p53 with the identical gene as well as the equivalent of a single letter base change. This changed the p53 protein and gave mutant cells an advantage over their neighbours.
They observed that the mutated cells grew rapidly and colonized the skin tissue, which became thicker in appearance. After six months the skin returned to normal and there was no visual difference between the normal skin and the mutant skin.
The investigators also analyzed the effect of sun exposure on cell mutations. Very low doses of ultraviolet light—below sunburn level—were shone onto the mice with mutated p53 genes. The mutated cells grew much faster. They reached the level of growth seen at six months in non-UV radiated clones in only a few weeks. Despite this rapid growth, the mice did not develop skin cancer nine months after exposure.
“We did not observe a single mutant colony of skin cells take over enough to cause cancer, even after exposure to ultraviolet light,” said joint first author Kasumi Murai, senior staff scientist at Wellcome Sanger Institute in Hinxton, U.K. “Exposure to sunlight continually created new mutations that outcompeted the p53 mutations. We found the skin looked completely normal after we shone UV light on the mice, indicating that tissues are incredibly well-designed to tolerate these mutations and still function.”
The investigators hypothesized that although exposure to sunlight can cause more cell mutations, it is just one of many possible factors that can lead to skin cancer diagnosis.
“The reason that people get non-melanoma skin cancer is because so much of their skin has been colonised by competing mutant cells over time. This study shows that the more we are exposed to sunlight, the more it drives new mutations and competition in our skin. Eventually the surviving mutation may evolve into a cancer,” explained senior author Ben Hall, PhD, computational biologist and group leader of the MRC Cancer Unit at the University of Cambridge.