University Scientists Find Gene Controlling Melanoma Spread

December 03, 1996

UNC-CH News Services

(Embargoed) CHAPEL HILL -- Scientists at Pennsylvania State University and the University of North Carolina at Chapel Hill School of Medicine have discovered a gene they called KiSS-1 that controls spread of an often deadly form of cancer known as malignant melanoma.

In work so far limited to laboratory mice, the researchers stopped the cancer from spreading by inoculating the animals with genetic material from human chromosome 6.

Their finding, which occurred in human cancer cells grown in the mice, should help doctors distinguish between melanomas that will colonize other organs and those that will not. Before long, the researchers say, it also might contribute to improved treatment for the illness, which is increasing across the United States.

A report on the findings appears in the Dec. 4 issue of the Journal of the National Cancer Institute.

Authors of the report include Drs. Jeong-Hyung Lee and Danny R. Welch, postdoctoral fellow and associate professor of pathology, respectively, at Penn State, and graduate student Karen Phillips and Dr. Bernard Weissman, associate professor of pathology, both at UNC-CH. The National Center for Human Genome Research's Dr. Jeffrey Trent helped with the study.

Weissman, a member of the UNC Lineberger Comprehensive Cancer Center, said the researchers found KiSS-1 on chromosome 1 and have not yet identified the master gene they know to be located on chromosome 6. He cautioned that cancers in humans could work differently.

"Still, if this indicates there are targets for therapy that would prevent human tumors from spreading from their original site, that would be a tremendous boon for therapy," he said.

Much research has focused on genes known as P53 and RBP16 that contribute to development of primary, or original tumors, the scientist said. Little is known about what genetic changes occur to allow cells from original tumors to enter the blood stream or lymphatic system and form secondary tumors throughout the body in a process known as metastasis.

Weissman and his colleagues used human melanomas in the mouse model just before spreading began. With the genetic material from human chromosome 6, they found they could prevent the cancer invasion almost entirely. In effect, they restored part of the normal function of the cancer cell that inhibits metastasis.

The next step will be to determine whether the gene, as they suspect, is absent or malfunctions in humans whose melanoma has spread, he said.

"If that's the case, we could start looking at what the gene's normal function is," Weissman said. "Then perhaps we could replace it or use compounds that mimic its function. This work should lead to a very good marker for determining if a cancer has already spread."

The new gene is the second tumor suppresser gene that has been identified, Weissman said. Dr. Patricia Steeg of the National Cancer Institute found the first, an apparently less potent form associated with breast cancer.

"The identification of metastasis-suppressing genes should have far-reaching implications for the diagnosis and treatment of disseminated cancer," wrote Drs. Isaiah J. Fidler and Robert Radinsky of the M.D. Anderson Cancer Center in an accompanying journal editorial. "However, translation of these findings to clinical reality still faces serious challenges."

By the time tumors are diagnosed, many appear to have different ways of spreading, and cells that can allow the cancers to spread may be masked.

"New therapeutic approaches directed toward increasing the expression of genes that suppress metastasis require detailed understanding of their regulation and function, a daunting task indeed," the two added. "Regardless of these formidable challenges, the new understanding of the molecular biology of cancer metastasis ... offers unprecedented opportunities for the inhibition and therapy of cancer metastasis. We are looking forward to these advancements."

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Note: Weissman's number is (919) 966-7533. To contact Welch, call Gail Brown at (717) 531-8604.

University of North Carolina at Chapel Hill

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