Wounds are capable of recruiting mutated stem cells to the site of injury thereby triggering basal cell carcinoma (BCC), reports a US study in the Proceedings of the National Academy of Sciences.

Aberrant wound healing with chronic inflammation is known to promote malignant transformation, with a variety of human cancers, including those arising from the lung, liver, pancreas, bone and skin associated with injury. Additionally, human BCCs have been observed at sites of vaccination, surgery, burns and other physical trauma.

In the current study Jeremy Reiter, and Sunny Wong, biochemists from the University of California, San Francisco, hypothesized that skin wounds may promote basal cell carcinoma, a form of skin cancer that arises from the cells of hair follicles.

For the study investigators created transgenic mice capable of producing follicular stem cells bearing the Smoothened (Smo) oncogene, which is known to sometimes be mutated in people with BCC. The gene could be switched on and off.

The investigators found that switching Smo on was not sufficient to trigger cancer in the mice. However, when the oncogene was activated in conjunction with damage to the skin, where mice were wounded by punching out a small disc of skin in their backs, they went on to develop BCC.  Small incisions similar to paper cuts also caused stem cells to form tumours nearby, but hair depilation had no effect. In the mice, mutated stem cells could still form tumours even if the injury came several weeks after the researchers introduced the mutations.

“These findings are concordant with step-wise models of cancer development, where long-lived progenitor cells residing in quiescent niches accumulate oncogenic insults before a final event exposes their tumorigenic phenotypes. Our work suggests that this final event need not be an additional mutation but can be wound induced mobilisation of oncogenically initiated stem cells,” write the authors.

In future studies, they add, it will be interesting to determine whether mobilisation of oncogene expressing stem cells underlies the development of other cancers whose pathogenesis has been associated with injury.

Reference

SY Wong, J F Reiter. Wounding mobilizes hair follicle stem cells to form tumors. PNAS doi 10.1073/pnas.1013098108