Skin is Surprisingly Resilient to Cancer

Human skin has evolved a greater resilience to cancer than other tissue types. It is an outcome that makes a certain amount of sense, given that skin is exposed to the additional mutational burden caused by solar radiation. Researchers here investigate some of the mechanisms involved in this cancer resistance, and suggest that the level of mutational damage is high enough that potentially cancerous mutations are continually being outcompeted by other potentially cancerous mutations. It is rare for any one mutant lineage to dominate sufficiently to generate skin cancer. The goal in this sort of investigation is to find something that could potentially serve as the basis for a cancer treatment. While this is fascinating, I don't immediately see the potential for any practical use of these findings.

Non-melanoma skin cancer in humans includes two main types: basal cell skin cancer and squamous cell skin cancer, both of which develop in areas of the skin that have been exposed to the sun. Basal cell skin cancer is the most common type of skin cancer, whereas squamous cell skin cancer is generally faster growing. However, every person who has been exposed to sunlight carries many mutated cells in their skin, and only very few of these may develop into tumours. The reasons for this are not well understood.

For the first time, researchers have shown that mutated cells in the skin grow to form clones that compete against each other. Many mutant clones are lost from the tissue in this competition, which resembles the selection of species that occurs in evolution. Meanwhile, the skin tissue is resilient and functions normally while being taken over by competing mutant cells.

Scientists used mice to model the mutated cells seen in human skin. Researchers focused on the p53 gene, a key driver in non-melanoma skin cancers. The team created a genetic 'switch', which when turned on, replaced p53 with the identical gene including the equivalent of a single letter base change. This changed the p53 protein and gave mutant cells an advantage over their neighbours. The mutated cells grew rapidly, spread and took over the skin tissue, which became thicker in appearance. However, after six months the skin returned to normal and there was no visual difference between normal skin and mutant skin.

The team then investigated the role of sun exposure on skin cell mutations. Researchers shone very low doses of ultraviolet light (below sunburn level) onto mice with mutated p53. The mutated cells grew much faster, reaching the level of growth seen at six months in non-UV radiated clones in only a few weeks. However, despite the faster growth, cancer did still not form after nine months of exposure. "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. We did not observe a single mutant colony of skin cells take over enough to cause cancer, even after exposure to ultraviolet light. Exposure to sunlight continually created new mutations that outcompeted the p53 mutations."

Link: https://www.sanger.ac.uk/news/view/skin-battlefield-mutations

Comments

Mmm... so this is some kind of hormesis and you need some level of solar radiation to promote mutations and avoid cancer...

Posted by: Antonio at October 1st, 2018 5:57 AM

@antonio

There could be some hormesis effect in play. After all, the areas with higher background radiation have slightly less cancer cases. However, in this case it seems that we have a curious way to tender most cancers none viable.

Unfortunately with cancer , even the chance of one out of billion could kill you since we have so many cells

Posted by: Cuberat at October 1st, 2018 1:05 PM

To add to the complexity of sun exposure and skin cancer:

Genome-wide association study in 176,678 Europeans reveals genetic loci for tanning response to sun exposure
https://kclpure.kcl.ac.uk/portal/en/publications/genomewide-association-study-in-176678-europeans-reveals-genetic-loci-for-tanning-response-to-sun-exposure%28a42df10e-1e77-46b8-82a0-67929fdfe60c%29.html

Beneficial skin bacteria protect against skin cancer
https://www.sciencedaily.com/releases/2018/03/180301103701.htm

I have a theory that wearing clothing causes skin cancer. It confuses and changes our skin microbiome, making it less protective against sun exposure. As for the face and arms, it could be due to use of soap changing the skin microbiome, and/or communication between bacteria throughout the body, making it less protective against sun exposure.

Half-in-jest, half-in-earnest!

Posted by: NY2LA at October 2nd, 2018 1:05 PM

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