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February 8, 2008 CHICAGO (Reuters) - A missing protein may explain why some skin cells advance to a deadly skin cancer known as melanoma instead of simply developing into harmless moles, U.S. researchers said on Thursday. They said a naturally secreted protein known as IGFBP7 prevents cells from developing into melanoma. The discovery could lead to better treatments for an often-deadly cancer. "This is part of our natural defenses to combat cancers," said Dr. Michael Green, a Howard Hughes Medical Institute researcher at the University of Massachusetts Medical School, whose study appears in the journal Cell. "What happens is this protein in melanomas gets shut off." Green said when they made a synthetic form of the protein and tried it on melanoma cells in the lab and on mice with melanoma, the cancers stopped growing. "The exciting result is that the melanoma still is sensitive to the protein IGFBP7," he said. "If we add it to melanomas, we kill them. That really suggests a way to kill these cancers," Green said in a telephone interview. He thinks the protein could be used as a targeted treatment for melanoma, a cancer he said is now "basically untreatable" once it has advanced. While melanoma accounts for only a small percentage of skin cancers, it accounts for most skin cancer deaths, killing more than 8,000 people in the United States last year. Melanoma is caused by the uncontrolled proliferation of pigment-producing skin cells called melanocytes. Moles or nevi, which are harmless, are also caused by abnormal growth of melanocytes. SEARCHING GENE BY GENE Green and colleagues knew that a mutation in a gene known as BRAF, which prompts cells to multiply abnormally, was frequently present in both moles and melanoma. They systematically disabled all the genes of cells with mutations of this BRAF gene in both melanoma and moles until they found the code responsible for this natural defense system. They turned up 17 genes, many of which were known to play a role in the life and death of cells. But they also found a protein known as IGFBP7. Green said it was intriguing because unlike many proteins which work on the inside of cells, this protein is secreted, allowing it to influence surrounding cells. In its cancer defense role, IGFBP7 tells its cell neighbors to ignore signals from the mutated BRAF gene to proliferate and instructs them instead to either hibernate or self-destruct. Green thinks some moles are artifacts of this process. When Green's team created a genetically modified version of this protein and injected it into the bloodstream of mice that had human melanoma tumors, the tumors stopped growing. They also found that samples of melanoma taken from people lacked the IGFBP7 protein. "It is a natural protein and a natural mechanism so we're encouraged by our mouse experiments that we were able to suppress the cancer without any apparent adverse reactions," Green said. "Obviously, we have to do a lot more tests," he added. Other human proteins have been shown to interfere with cancer but researchers have encountered problems in manufacturing and finding safe ways to give them to patients. Copyright 2008 Reuters. Click for Restrictions.
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