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Of Mice and Melanoma

Researchers graft human skin onto mice and trigger deadly skin cancer

SATURDAY, May 26, 2001 (HealthDayNews) -- To better understand the mechanisms that cause melanoma, researchers have grafted human skin onto the backs of mice, exposed them to ultraviolet light and triggered the deadly skin cancer.

"It's the first time that anybody's induced a human melanoma in skin," says lead author Dr. Carola Berking, a dermatologist and postdoctoral fellow at The Wistar Institute in Philadelphia.

She and her colleagues used pieces of foreskins from newborns or breast skin from adult donors who had undergone plastic surgery. The pieces of skin were 1-to-3 centimeters in length.

In order to accelerate a disease process thought to unfold over many years, the researchers used gene therapy to induce overproduction of a naturally occurring growth factor, known as basic fibroblast growth factor (bFGF).

"This growth factor is a natural factor we have everywhere in our body," Berking says.

The mice were exposed to ultraviolet B (UVB) rays three times a week for two months. She compared the UV exposure received by the mice to a mild sunburn on humans.

All the mice showed a variety of pathological changes in the human skin grafts that are known to be melanoma precursors, and one mouse actually developed melanoma. Berking says the others would have developed melanoma as well, if given more time.

It's the combination of overproduction of bFGF and exposure to UVB that's the key here, Berking says. The growth factor bFGF occurs naturally in human skin but its regulation can be affected by a wound or inflammation, she adds.

"We claim that any disregulation of growth factors in combination with UV can induce transformation of melanocytes, which can lead to melanoma," Berking says.

Melanocytes are cells that make the brown pigment called melanin.

The study was published in a recent issue of the American Journal of Pathology.

It's important to be able to work with human skin in this kind of research, Berking says. It's usually done with mice or other laboratory animals, but "human skin really differs from skins of any other animals. Especially the pigment cells. In human skin, they're located in the epidermis -- or upper skin -- and not in the hair follicles, as with animals."

Meenhard Herlyn, the study's senior author and chairman of the tumor biology program at The Wistar Institute, adds, "The overall summary is, yes, sunlight has a major role [in melanoma], but potentially not the only role. Additional factors have to come in it.

"What we are saying is that, yes, ultraviolet light, the way it is coming from the sun, can induce tumors and we can speed it up by using a normal physiological factor everyone has," Herlyn adds.

Dr. Martin A. Weinstock, chairman of the American Cancer Society's skin cancer advisory group, says the Wistar research doesn't contribute greatly to public health measures to protect people from melanoma and other skin cancers. But "it's potentially important in better understanding melanoma and mechanisms related to melanoma," he says.

Weinstock says the melanoma-UV link has been long established by extensive epidemiological studies.

"It [the Wistar research] sounds like it's interesting because it's a different way of inducing melanoma in an animal model, and it may be useful for understanding what's going on," Weinstock adds.

What To Do

There are an estimated 47,000 new cases of melanoma each year in the United States and about 7,700 deaths from the disease. Melanoma accounts for 4 percent of skin cancer cases but is responsible for 79 percent of skin cancer deaths.

For more HealthDay stories on the dangers of ultraviolet radiation in sun light, click here.

You can learn more about melanoma at MelanomaNet. To find more information about all types of skin cancer and how to protect yourself, see the American Cancer Society Web site.

SOURCES: Interviews with Carola Berking, M.D., dermatologist and postdoctoral fellow; Meenhard Herlyn, D.V.M., professor and chair of program for tumor biology; both at The Wistar Institute, Philadelphia, Pa.; Martin A. Weinstock, M.D., Ph.D., professor of dermatology, Brown University, Providence, R.I., and chair of the skin cancer advisory group, American Cancer Society: March 2001 issue, American Journal of Pathology.
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