Skin Cancers Traced to Previously Unknown Effect of UV Radiation ▲ NCI Cancer Bulletin for July 10, 2012 - National Cancer Institute

NCI Cancer Bulletin for July 10, 2012 - National Cancer Institute

Skin Cancers Traced to Previously Unknown Effect of UV Radiation

The harmful effects of the sun on the outer layer of skin (the epidermis) are well documented. But ultraviolet (UV) radiation from the sun also may alter cells in the underlying layer of skin (the dermis), setting the stage for the development of cancer in the epidermis, according to findings published June 8 in Cell.
In the study, researchers observed epidermal changes in mice that were similar to those seen in UV-induced human premalignant skin lesions called actinic keratosis, which can progress to squamous cell carcinoma, the most common skin cancer in humans. In the mice, the Notch signaling pathway was lost in stromal cells, which contribute to the dermal compartment of the skin.
The loss of Notch signaling appeared to be sufficient for tumors to emerge in the overlying epidermis, the researchers observed. The increased inflammation that accompanied the loss of Notch signaling also may have played a role in tumor development, they added.
"This study says that changes in the stroma are as important as changes in the epidermis, and we probably need to pay attention to them," said lead investigator Dr. G. Paolo Dotto of Massachusetts General Hospital and the University of Lausanne, Switzerland.
To investigate the clinical relevance of the mouse findings, the researchers analyzed tissue from human patients with actinic keratosis. They found that Notch signaling was reduced in human stromal cells near precancerous lesions. Moreover, similar molecular changes were induced by UVA radiation, which is an environmental cause of skin cancer, the study authors noted.
The findings may provide insights into the phenomenon of field cancerization, in which a patch or field of cells, rather than a single initiating cell, changes when exposed to a carcinogen and has the potential to become premalignant, Dr. Dotto pointed out.
In an accompanying editorial, Drs. Sakari Vanharanta and Joan Massagué of Memorial Sloan-Kettering Cancer Center praised the study for raising the possibility that, in addition to causing mutations, UV radiation may lead to tumor-promoting changes in dermal cells.
The findings add to the extensive list of harmful effects of excessive sun exposure. "This should give [people] one more reason to cover up," wrote Drs. Vanharanta and Massagué.