Studies in mice suggest tumor-triggering mechanism only occurs in full-thickness wounds.
Scientists at Sweden’s Karolinska Institutet may have thrown new light on the mechanisms by which chronic wounds and acute trauma can act as increased risk factors for the development of basal cell carcinomas (BCCs). Their studies in mice suggest the tumor-promoting effect of the wound environment is due to the recruitment of tumor-initiating cells originating from neighboring hair follicles. Their work is published in the early online edition of PNAS, in a paper titled, “Wounding enhances epidermal tumorigenesis by recruiting hair follicle keratinocytes.”
Although chronic wounds are a well-recognized risk factor for cancer formation, little is known about the molecular and cellular mechanisms underlying this effect, notes Karolinska Institutet professor Rune Toftgård, Ph.D., and colleagues. To try and further define these mechanisms, the researchers used three different transgenic mouse models for human BCC and an approach known as lineage tracing to determine where and in which cells tumor formation starts.
Their results showed that the wound environment can enhance the development of BCC via two distinct mechanisms: promotion of tumor growth, and enhancement of tumor initiation frequency. Essentially, as a result of the wound-healing process, hair follicle stem cells and their daughter cells present in the nonfollicular part of the skin, the interfollicular epidermis, acquire the ability to initiate tumor formation in their new location.
Importantly, the studies showed that damage to deeper parts of the skin is required to elicit the tumor-enhancing effect. “Only full-thickness wounds induce the migration of cells from neighboring hair follicles to the place of injury,” they report. “One may assume that the combination of tissue damage from severe sunburn, and DNA damage or mutations caused by UV radiation, has a similar effect,” Dr. Toftgård adds.