Skin wounds trigger tumors

Even small wounds like paper cuts can activate cancer-provoking genes in the skin as it heals, leading to an increased risk of the most commonly diagnosed cancer, according to a study published online today (February 14) in the Proceedings of the National Academy of Sciences.

Inactive stem cells (green) reside at the bottom of hair follicles but can be recruited to a wound site to help with the healing process.
Image: Jeremy Reiter and Sonny Wong, UCSF

The work is "pioneering," said Ervin Epstein, a cancer researcher at the Children's Hospital Oakland Research Institute in California, who was not involved in the research. "What could be more important than identifying the cell of origin of the most common of human cancers?" Basal cell carcinoma is a type of skin cancer that frequently arises from the cells of hair follicles, which contain stem cells that differentiate and divide to replace the hair after it falls out. If these follicular cells accumulate errors in the DNA that regulates their division, they can spawn tumorous growth.Although the follicular stem cells function mainly in hair growth, injuries to the surrounding skin can recruit these stem cells to aid in the healing process. Given that various types of injuries, from surgical incisions to stomach ulcers, have been linked to cancer, Jeremy Reiter, a biochemist at the University of California, San Francisco, and his postdoc Sunny Wong hypothesized that skin wounds may promote basal cell carcinoma. Reiter and Wong to took skin biopsies of laboratory mice to induce topical injuries. As the stem cells from the hair follicles migrated to the wound site to help heal the injury, Reiter and Wong found that the cells expressed high levels of the oncogenes commonly found in basal cell carcinomas. Sure enough, after 10 weeks, the researchers saw the formation of basal cell carcinoma-like tumors in the injured mice, suggesting that this type of skin cancer could be triggered by an injury and subsequent migration of follicular stem cells. "It's been well-known that the skin mobilizes cells from the hair follicles" to heal injuries, Epstein said. "What Wong and Reiter showed is that if you mobilize these cells into the epidermis, they can produce tumors."Reiter said that over the past 10 years, more and more scientists have begun to think that "cancers are wounds gone awry." Normally, the hair follicle represses the tumor-generating potential of the stem cells, he said, "but when these cells leave their niche, the reins that are supplied by the [follicle] come off. "The development of basal cell carcinomas wasn't limited to relatively major wounds like skin biopsy. Even small incisions could induce carcinomas, the researchers found.But Reiter cautions that these results aren't a cause to panic over every single paper cut. Although basal cell carcinomas may originate from improper wound healing, Reiter said, only a tiny fraction of injuries ever generate cancer. "These results give us an understanding of how the normal healing process can become co-opted to promote tumors," Reiter said.S.Y. Wong and J.F. Reiter, "Wounding mobilizes hair follicle stem cells to form tumors," PNAS, www.pnas.org/cgi/doi/10.1073/pnas.1013098108, 2011.
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