Researchers from the Perelman School of Medicine at the University of Pennsylvania have uncovered a skin cell predominantly infected by the Merkel cell polyomavirus, which can cause Merkel cell carcinoma (MCC), a lethal form of skin cancer.
Through the findings, using dermal fibroblasts, researchers developed a cell culture model for the viral infection that may help further investigation about the cancer pathogenesis. The research suggests that the FDA-approved drug trametinib, indicated for melanoma, could be an effective inhibitor of viral infection.
The research paper, “Identifying the Target Cells and Mechanisms of Merkel Cell Polyomavirus Infection,” was published in Cell Host & Microbe.
Infection by the Merkel cell polyomavirus, a benign virus usually found in the skin, can cause Merkel cell carcinoma (MCC) in immune-compromised individuals. MCC is a less common type of skin cancer, but is more likely to spread to other parts of the body if it is not caught in time, which makes MCC one of the most dangerous and difficult-to-treat skin cancers.
According to the American Cancer Society, about 1,500 cases of MCC are diagnosed in the United States each year. Risk factors for MCC include excessive sunlight and ultraviolet radiation, immunosuppression and old age. The mortality rate for MCC is 33% with a 45% five-year survival rate.
In the recent study, researchers identified special enzymes called matrix metalloproteinases as stimulators of the Merkel cell polyomavirus infection.
“This suggests that Merkel cell carcinoma risk factors such as ultraviolet radiation and aging, which are known to stimulate the expression of these metalloproteinase enzymes, may promote viral infection and thus drive the development of cancer,” said senior author Jianxin You, in a press release.
These enzymes are usually activated in the re-engineering of the skin during healing. After a specific aggression, such as excessive sunlight, the enzymes are activated, destroying the extracellular matrix of affected cells.
Researchers found that the FDA-approved drug trametinib, for melanoma and other cancers, stops Merkel cell polyomavirus’ transcription and replication, blocking the viral infection. Low doses of the drug were able to wipe out the infection in the cell culture model while not affecting the normal control cells.
“Building on this novel cell culture model for Merkel cell polyomavirus infection, we would like to establish an animal model to elucidate the mechanisms by which Merkel cell polyomavirus infection leads to the highly aggressive Merkel cell carcinoma,” said first author Wei Liu.