Protein Key to Skin Cancer Spread Found

Researchers say it's a possible target for treatment

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By
HealthDay Reporter

THURSDAY, March 17, 2005 (HealthDay News) -- A study of children with a particularly nasty skin disease has identified a protein that enables the deadly spread of a common skin cancer.

The protein is collagen VII, one of a family of molecules that play an essential role in skin culture, says a report in the March 18 issue of Science by researchers at the Stanford University School of Medicine. Collagen VII normally keeps the outer layer of the skin anchored to the inner layer.

The researchers studied 12 children with a rare blistering skin condition called recessive dystrophic epidermolysis bullosa, which affects the bottom layer of the skin and causes not only persistent blistering, but also webbing of the fingers and toes that can require surgery.

About two-thirds of the children with the condition develop squamous cell carcinoma, the second most common skin cancer, with more than 200,000 new cases in the United States each year.

Taking tissue samples from the 12 children, Dr. Paul Khavari, a professor of dermatology at Stanford, and Dr. Susana Ortiz-Urda, a postdoctoral scholar, found that samples from four of them did not become cancerous even when molecular cancer-causing mechanisms were activated. Samples from the other eight children did turn cancerous.

Molecular studies showed that the four children whose samples did not become cancerous had a genetic mutation that caused them to have no collagen VII at all. Samples from the other children, with different mutations that produced a fragment of collagen VII, did develop into squamous cell carcinoma.

That work was done in lab tissues. The Stanford researchers then checked out the finding by transplanting human skin cancer cells into mice. Treating the mice with an antibody that blocked collagen VII prevented the cancer cells from spreading.

At least a fragment of collagen VII is required for skin cancer cells to break free and start their potentially deadly spread, Khavari said. "When we blocked this sequence, we also blocked the cancer from spreading," he added.

Two possible explanations of the effect were offered by Dr. Ervin H. Epstein Jr., a professor of dermatology at the University of California at San Francisco, and co-author of an accompanying commentary.

"One is that in order to invade surrounding tissue, cancer cells must be able to hold on," he said. "Maybe they can't hold on tightly enough. But cancer cells respond to their external environment. Without collagen VII, they could be deaf to the surrounding signals that should be given to the cells."

Epstein said he sees a "glimmer" of possible medical uses of the finding, "but whether there are immediate possibilities, I don't know."

Targeting the molecule with antibodies that would counteract its activity or prevent cancer cells from making it might help prevent their spread, "but if the skin fell off, that would not be so good," Epstein said.

Any medical application might be a "Pyrrhic victory," in which more is lost than gained, Epstein wrote, "perhaps winning the battle against squamous cell carcinoma but losing the battle against the disfiguring skin defects of dystrophic epidermolysis bullosa."

More information

The facts about squamous cell carcinoma are explained by the Skin Cancer Foundation.

SOURCES: Paul Khavari, M.D., Ph.D, professor, dermatology, Stanford University School of Medicine, Stanford, Calif.; Ervin H. Epstein, Jr., professor, dermatology, University of California, San Francisco; March 18, 2005, Science

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