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Blocking Protein May Help Protect Against Skin Cancers

Posted: March 12, 2009

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“Our data show that MIF appears to be affecting multiple pathways that are important for tumor generation and progression. It also is clear here that there is a link between inflammation and cancer,” said Abhay Satoskar, associate professor of microbiology at Ohio State University and a coauthor of the study. “No one else has shown this in a skin cancer model.”

The scientists exposed normal mice and mice deficient in MIF to ultraviolet B light, the type of radiation from the sun that damages the skin. The mice were exposed to the light three days per week for 46 weeks, with doses increased regularly after week 13 to account for skin adaption to UVB exposure. The exposure in the study was designed to accelerate tumor growth and far exceeded the UVB exposure that humans experience over the same time period.

By week 37, more than two-thirds of the mice exposed to UVB light had developed at least one tumor, and all mice had developed tumors by week 45. The MIF-deficient mice averaged 2.89 tumors per mouse at the end of the exposure, compared to an average of 5.27 tumors per normal mouse. Overall, the MIF-deficient mice on average had about half as many tumors and significantly smaller tumors than did the normal mice. The tumors on the MIF-deficient mice were also less likely to be malignant than were tumors on normal mice.

Satoskar and colleagues compared a number of tumor characteristics on the two groups of UVB-exposed mice to confirm the MIF deficiency’s role in lowering the incidence of skin cancer. The MIF-deficient mice had almost twice as many tumor-suppressor cells of the p53 gene than did normal mice, suggesting that the presence of the MIF protein interferes with this tumor suppressor’s ability to do its work.

The MIF-deficient mice also had lower concentrations of the protein vascular endothelial growth factor (VEGF) than did normal mice. VEGF has previously been found to promote the development of blood vessels in certain types of cancer tumors, so the lower amount of the protein in MIF-deficient mice means the tumors they did develop had less vascular support to grow, Satoskar said. Finally, MIF-deficient mice exposed to UVB rays had lower levels of three markers for inflammation, indicating an important link between MIF and the inflammatory response in skin that follows UVB exposure.