EU-funded researchers uncover origins of skin cancer
EU-funded researchers have identified the cells that are at the origin of the most common form of skin cancer. Writing in the journal Nature Cell Biology, the researchers explain that basal cell carcinoma arises in the skin cells between hair follicles, and not in the hair follicles themselves, as was previously assumed. The findings not only shed light on the origins of skin cancer, but highlight the difficulties faced by researchers seeking to uncover the roots of other kinds of cancer. EU support for the work came from the Seventh Framework Programme (FP7) via a Starting Independent Researcher Grant from the European Research Council (ERC). The question of precisely which kinds of cells turn cancerous is an important one in biology, and for most kinds of cancer, the cells that give rise to the tumour remain unknown. Most efforts in this area focus on stem cells. Stem cells survive and divide in tissues for a long time, raising the likelihood that they will undergo a mutation that could cause cancer. In this study, scientists at the Université Libre de Bruxelles (ULB) and Université Catholique de Louvain (UCL) in Belgium studied basal cell carcinoma in mice. Basal cell carcinoma is the most common form of skin cancer in humans, affecting over a million people worldwide every year. The skin is made up of different kinds of cells: those that make up hair follicles, sebaceous glands and the interfollicular epidermis, which lies between the hair follicles, all look very different to one another. Basal cell carcinoma cells bear a strong morphological and biochemical resemblance to hair follicles, and this had led researchers and doctors alike to assume that the cancer must arise in hair-follicle stem cells. To ascertain if this was the case, the researchers developed a new method to find out precisely where the cancer originated. They activated cancer genes in different kinds of skin cells in mice and waited to see which cells would go on to become cancerous. To their surprise, activating cancer genes in hair-follicle stem cells did not trigger tumour formation. Instead, the source of skin cancer turns out to be the resident stem cells of the interfollicular epidermis. 'This was really surprising,' commented the lead author of the paper, Khalil Kass Youssef of the ULB. 'We were expecting that this cancer would arise from hair-follicle stem cells and when we realised that what is written in text books and taught to medical students was challenged by our findings, we were really excited.' In addition to uncovering the true origins of basal cell carcinoma, the team also demonstrated that all the interfollicular epidermis stem cells targeted in the experiment eventually progressed into invasive basal cell carcinoma. This suggests that once a cancer gene has been activated in a long-lived stem cell, no further genetic events are needed for the cancer to develop. The researchers noted that the new findings also make sense when one considers the strong link between skin cancer and exposure to ultraviolet (UV) light. UV light does not penetrate far into tissue, and so is actually much more likely to cause DNA damage in interfollicular epidermis cells than in hair-follicle bulge stem cells that lie much deeper in the skin. The results do not just light on the origins and development of skin cancer alone. The scientists conclude: 'This finding could be important for other cancers as well, as it clearly demonstrates that the biochemical and morphological characterisations of tumour cells can be misleading in identifying the cells at the origin of cancer.' Most cases of basal cell carcinoma are caused by excessive exposure to UV rays from the sun. Fortunately it is relatively easy to treat, and the vast majority of patients go on to make a full recovery.
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